iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression

iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression

NSC 16186 No. of Pages 73 22 April 2015 Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsyna...

5MB Sizes 0 Downloads 32 Views

NSC 16186

No. of Pages 73

22 April 2015 Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006 1

Neuroscience xxx (2015) xxx–xxx

4

ITRAQ-BASED QUANTITATIVE ANALYSIS OF HIPPOCAMPAL POSTSYNAPTIC DENSITY-ASSOCIATED PROTEINS IN A RAT CHRONIC MILD STRESS MODEL OF DEPRESSION

5 6 7

X. HAN, a,b,c  W. SHAO, a,b,c  Z. LIU, a,b,c S. FAN, a,b,c J. YU, b,c J. CHEN, b,c R. QIAO, b,c J. ZHOU b,c* AND P. XIE a,b,c,d*

8 9

a Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China

2 3

10 11

b Institute of Neuroscience, Chongqing, China

12

c

13 14

d

Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China

15

Abstract—Major depressive disorder (MDD) is a prevalent psychiatric mood illness and a major cause of disability and suicide worldwide. However, the underlying pathophysiology of MDD remains poorly understood due to its heterogenic nature. Extensive pre-clinical research suggests that many molecular alterations associated with MDD preferentially localize to the postsynaptic density (PSD). Here, we used a rodent chronic mild stress (CMS) model to generate susceptible and unsusceptible subpopulations. Proteomic analysis using an isobaric tag for relative and absolute quantitation (iTRAQ) and tandem mass spectrometry was performed to identify differentially expressed proteins in enriched PSD preparations from the hippocampi of different groups. More than 1500 proteins were identified and quantified, and 74 membrane proteins were differentially expressed. Of these membrane proteins, 51 (69%) were identified by SynaptomeDB search as having a predicted PSD localization. The unbiased profiles identified several PSD candidate proteins that may be related to CMS vulnerability or insusceptibility, and these two CMS phenotypes

Chongqing

Medical

displayed differences in the abundance of several types of proteins. A detailed protein functional analysis pointed to a role for PSD-associated proteins involved in signaling and regulatory functions. Within the PSD, the N-methyl-D-aspartate (NMDA) receptor subunit NR2A and its downstream targets contribute to CMS susceptibility. Further analysis of disease relevance indicated that the PSD contains a complex set of proteins of known relevance to mental illnesses including depression. In sum, these findings provide novel insights into the contribution of PSD-associated proteins to stress susceptibility and further advance our understanding of the role of hippocampal synaptic plasticity in MDD. Ó 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

University,

Chongqing Key Laboratory of Neurobiology, Chongqing, China

Key words: major depressive disorder, chronic mild stress, hippocampus, postsynaptic density, iTRAQ, proteomics. 16

*Correspondence to: J. Zhou, Institute of Neuroscience, Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing 400016, China. P. Xie, Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, No. 1 Yixue Road, Yuzhong District, Chongqing 400016, China. Tel: +86-23-68485490; fax: +86-23-68485111. E-mail addresses: [email protected] (J. Zhou), xiepeng@ cqmu.edu.cn (P. Xie).   These authors contributed equally to this work. Abbreviations: 2DE, two-dimensional gel-electrophoresis; ANOVA, analysis of variance; BCA, bicinchoninic acid; BSA, bovine serum albumin; CMS, chronic mild stress; DAVID, database for annotation, visualization and integrated discovery; FASP, filter-aided sample preparation method; FDR, false discovery rate; FST, forced swim test; GO, gene ontology; GRAVY, grand average hydropathicity; HCD, higher energy collisional dissociation; iTRAQ, isobaric tag for relative and absolute quantitation; MDD, major depressive disorder; MW, molecular weight; NMDA, N-methyl-D-aspartate; Nrgn, neurogranin; pI, isoelectric point; PSD, postsynaptic density; SCX, strong cation exchange; SPT, sucrose preference test; TMDs, transmembrane domains; UniProt, universal protein resource. http://dx.doi.org/10.1016/j.neuroscience.2015.04.006 0306-4522/Ó 2015 IBRO. Published by Elsevier Ltd. All rights reserved. 1

INTRODUCTION

17

Major depressive disorder (MDD) is a common and debilitating mental illness affecting approximately 2.5% of the general population and is predicted to be the number two cause of illness worldwide by 2020 (Lecrubier, 2001). Symptoms of the illness include cognitive impairment and memory loss, implicating synaptic dysfunction in the pathophysiology of MDD (Levens and Gotlib, 2009; Barabassy et al., 2010; Boyle et al., 2010). This possibility is supported by animal studies demonstrating a reduction of dendritic spine numbers and hippocampal neuronal function (Radley et al., 2006; Liu and Aghajanian, 2008). Postmortem studies have suggested that somatodendritic, axonal, synaptic, and glial cell number changes are all involved in the inhibition of adult hippocampal neurogenesis (D’Sa and Duman, 2002; Sheline et al., 2003; Pittenger and Duman, 2008; Lorenzetti et al., 2009). This is also consistent with brain imaging studies that have reported a reduction in hippocampal volume in postmortem animal models of either stress or depression (D’Sa and Duman, 2002; Pittenger and Duman, 2008). In animal models, stress-induced hippocampal neuropathological changes may be summarized as follows: loss of dendritic spines, decrease in the number and length of dendrites, loss of synapses, loss of glia, and the impairment of neurogenesis (D’Sa and Duman, 2002; Sheline et al., 2003; Pittenger and Duman, 2008). To date, however, the protein substrates involved in synaptic plasticity in the hippocampus of

18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45

NSC 16186

No. of Pages 73

22 April 2015

2 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

MDD have not been well-explored (Czeh and Lucassen, 2007). Recent studies have used molecular profiling technologies to examine the brains of postmortem depressed patients and rodent models of depression. Several groups have used microarray approaches to demonstrate abnormalities in the expression of transcripts related to synaptic transmission, particularly glutamate and GABAergic signaling, in the brains of depressed patients with or without suicide, especially in the frontal and limbic regions (Choudary et al., 2005; Sequeira et al., 2007, 2009; Klempan et al., 2009). A number of proteomic studies investigating the overall level of hippocampal tissue from various stress systems have shown that stressful events alter the expression of proteins with roles in energy metabolism, neurogenesis, synaptic plasticity, and neurotransmission (Martins-de-Souza et al., 2010; Martins-de-Souza et al., 2012a,b). Although it is unclear whether altering these molecular dysregulations can affect overall hippocampal structure and function, there is evidence that significant changes occur at the subcellular level, particularly at neuronal synapses. Because of the complexity of the central nervous system, the uses of fractionation enrichment techniques are usually necessary to achieve a reliable quantitation of low-abundance proteins. Within the synapse, the postsynaptic site contains a high concentration of proteins, including receptors and their intracellular signaling components that receive and transduce synaptic information. This postsynaptic electron-dense structure, termed the postsynaptic density (PSD), is a highly-organized structure attached to the postsynaptic neuronal terminal and is comprised of a complex network of cytoskeletal scaffolding and signaling proteins. These proteins facilitate the movement of receptor and signaling complexes. The PSD is critical to normal neurotransmission but is also critical to adaptive behaviors such as learning and memory. It has been strongly implicated in neuropsychiatric disorders (Jay et al., 2004), such as MDD, through its roles in synaptic plasticity and cognitive function (Duric et al., 2013). Although constituents of the PSD have been implicated in MDD using conventional detection techniques (Kinnunen et al., 2003; Duric et al., 2013), no study has yet focused on exploring global changes in the hippocampal PSD fraction through the use of a high-throughput proteomic screen. In this study, using quantitative proteomics, we examined changes in the expression levels of hippocampal PSD-associated proteins in a chronic mild stress (CMS) rat model of depression. This model generates CMS-susceptible and unsusceptible subpopulations, reflecting the two hedonic responses to CMS. To measure the relative changes in protein expression, we used isobaric tag for relative and absolute quantitation (iTRAQ) followed by tandem mass spectrometric (LC-MS/MS) analysis. Our large-scale subcellular proteome profiles identified several differential PSD-associated proteins that may be specifically related to stress vulnerability. These data should provide a valuable resource for deciphering the

molecular mechanism(s) underlying synaptic plasticity observed in MDD.

the

abnormal

EXPERIMENTAL PROCEDURES

107 108

109

Ethics statement

110

This study was approved by the Ethics Committee of the Chongqing Medical University (Chongqing, China), and all procedures of animal care and treatment were in accordance with the National Institutes of Health Guidelines for Animal Research (Guide for the Care and Use of Laboratory Animals). Special care was taken to minimize the number and suffering of animals.

111

Animals and CMS treatment

118

Eighty-one healthy adult male Sprague–Dawley rats, purchased from the animal facility at the Chongqing Medical University (Chongqing, China), were housed individually, given access to food and water ad libitum, and maintained on a 12-h light/dark cycle (light from 7:30 to 19:30) at a constant temperature of 21–22 °C and humidity of 55 ± 5% (unless otherwise noted). Animal weight was approximately 165 g when adaptation for sucrose consumption was initiated and approximately 250 g at the start of the stress regime. The rats were allowed one week to acclimate to the environment and then 1% sucrose solution was given to them, as well as water for five weeks for sucrose habituation. During this period, sucrose preference of all rats was tested twice weekly during the first three weeks and once weekly during the last two weeks. According to the sucrose intakes of the three final baseline tests, the rats were divided randomly into two groups and placed in separate rooms. Stress groups were exposed to a four-week CMS procedure, whereas the control group was left undisturbed. The CMS protocol was performed according to the procedure described in our previous studies (Hu et al., 2013; Yang et al., 2013). In short, rats were subjected to a variety of mild stress factors: paired housing, a 45° cage tilt along the vertical axis, a soiled cage (with 300 ml water spilled into bedding), exposure to an empty water bottle immediately following a period of acute water deprivation, stroboscopic illumination (300 flashes/min), continuous overnight illumination, and white noise. The procedure including the time and length of stressors are described in Appendix Table 1. At the end of every week, the sucrose preference of all of the rats was assessed, and the forced swim test (FST) was carried out in the final week.

119

Sucrose preference test (SPT)

154

The SPT was conducted as a measure of the anhedonic effect of CMS. A two-bottle preference test was used, where the rats had access to both water and a 1% sucrose solution for 24 h during a no-stress period. The positions of the two bottles (on the left and right sides of the cages) were randomly varied. All fluid consumption was recorded by weighing the two bottles before testing and after 24 h. The sucrose preference was calculated

155

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

112 113 114 115 116 117

120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153

156 157 158 159 160 161 162

NSC 16186

No. of Pages 73

22 April 2015

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

165

according to the preference = sucrose (g) + water intake (g)).

166

FST

Extraction and digestion of proteins

220

167

The FST was performed as described previously with slight modifications (Porsolt et al., 1977). The rats were placed individually in a cylinder (40 cm in height  20 cm in diameter) filled with water (24 ± 1 °C) to a height of 30 cm. A 15-min pretest period was followed 24 h later by a 5-min test period during which the total immobility time was recorded. The test was monitored by a video surveillance system. Water in the cylinders was changed before each trial.

The obtained PSD pellet was dissolved using a sample buffer (4% SDS, 10 mM DTT, 150 mM Tris–HCl, pH 8.0). The lysate was boiled in water for 5 min and then centrifuged at 40,000g for 15 min. Protein concentrations were determined using a bicinchoninic acid (BCA) protein assay kit according to the manufacturer’s instructions (Pierce, USA). Bovine serum albumin (BSA) was used as the standard. Subsequent protein digestion was performed using the filter-aided sample preparation method (FASP) in a 10-kDa molecular weight cut-off centrifugation filter (Sartorius) (Wisniewski et al., 2009a,b). The sample was diluted with 200 ll of UA buffer (8 M urea, 150 mM Tris–HCl, pH 8.0) and then centrifuged at 14,000g for 30 min. This step was repeated once. Then, 100 ll of 50 mM iodoacetamide in UA buffer was added to the filters, and the samples were incubated in darkness for 30 min. Filters were washed twice with 100 ll of UA buffer followed by two washes with 100 ll of dissolution buffer (50 mM triethylammonium bicarbonate, pH 8.5). Proteins were digested overnight in a 40 ll dissolution buffer using trypsin (Promega) at an enzyme-to-protein ratio of 1:50 at 37 °C. The released peptides were collected by centrifugation at 14,000g for 10 min followed by two washes with dissolution buffer.

221

iTRAQ labeling and strong cation exchange (SCX) fractionation

245

The tryptic peptides were labeled with an iTRAQ-8plex kit (Applied Biosystems) according to the manufacturer’s protocol. Samples from the control group were labeled with reagents 115 and 118, samples from the susceptible group were labeled with reagents 114 and 117, and samples from the unsusceptible group were labeled with reagents 113 and 116. The incubation was allowed to proceed at room temperature for 2 h and then stopped by the addition of 10 mM KH2PO4, 25% ACN, pH 3.0. Subsequently, all the three labeledsamples were pooled, vacuum-dried and further fractionated offline using SCX chromatography. Briefly, the peptides were dissolved and loaded onto a Polysulfoethyl 4.6  100 mm column (5 lm, 200 A˚, PolyLC Inc., MD, USA) at a flow rate of 1 ml/min. A suitable gradient elution was applied to separate peptides at a flow rate of 1 ml/min with elution buffer (10 mM KH2PO4, 500 mM KCl in 25% acetonitrile, pH 3.0). Eluted peptides were collected and desalted by an offline fraction collector. The resulting 30 fractions were combined to 10 pools and desalted on C18 Cartridges (Emporeä SPE Cartridges C18 (standard density), bed I.D. 7 mm, volume 3 ml, Sigma, St. Louis, MO, USA). Each final fraction was concentrated by a vacuum concentrator and reconstituted with 40 ll of 0.1% formic acid for LC-MS/MS analysis.

247

163 164

168 169 170 171 172 173 174 175

following formula: sucrose intake (g)/(sucrose intake

3

176

Statistical analysis of SPT and FST data

177

Statistical analyses were carried out using SPSS 16.0. Data from the SPT and FST were analyzed by a oneway repeated measured analyses of variance (ANOVA) followed by a post hoc LSD test. A p-value of less than 0.05 was considered to be statistically significant. Statistics were presented as mean ± standard errors (SE).

178 179 180 181 182 183

184

Preparation of hippocampal PSD fractions

185

PSD fractions were obtained using a biomedical method essentially as previously reported (Phillips et al., 2001; Abul-Husn et al., 2009; Hu et al., 2013; Focking et al., 2014). Rats were sacrificed by decapitation and the brains rapidly removed. The fresh hippocampal tissue samples were collected and pooled. Using a motor-operated Teflon-glass grinder, the pooled tissues were homogenized on icein solution A (0.32 M sucrose, 1 mM MgCl2, and 0.1 mM CaCl2) containing a protease inhibitor cocktail (Sigma–Aldrich, St. Louis, MO, USA), respectively. All the following fractionation steps were carried out at 4 °C unless otherwise specified. Homogenates were centrifuged at 1400g for 10 min, and the resultant pellet was then homogenized again. The second centrifugation was performed at 710g for 10 min. Supernatants were pooled and centrifuged at 12,000g for 30 min. The resulting pellet was suspended for a second time in solution B (0.32 M sucrose and 0.1 mM CaCl2) then layered over the 1.2 M/1.0 M/0.85 M sucrose gradient (10 ml each). After ultracentrifugation (himac cp 80 wx, Hitachi Koki, Japan) at 82,500g for 2 h, the synaptosome fraction from the 1.2 M/1.0 M interface was collected. To obtain PSD fractions, an aliquot solution (synaptosomal fraction) was diluted with ice-cold 0.1 mM CaCl2 and brought to an equal volume of 2hypotonic buffer (40 mM Tris–HCl pH 8, 2% Triton X-100, 0.2 mM CaCl2) containing protease and phosphatase inhibitor cocktails. This solution was mixed by inversion and incubated on a shaker for 20 min at 4 °C. The PSD pellet was collected by centrifugation at 40,000g for 20 min at 4 °C and then stored at 80 °C before use in the proteomic analysis. The following iTRAQ-labeling proteomic experiment was conducted on six sample pools corresponding to the three groups

186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217

with each pool originating from three or four rats (Henningsen et al., 2012; Hu et al., 2013).

218

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

219

222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244

246

248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272

NSC 16186

No. of Pages 73

22 April 2015

4

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

273

LC-MS/MS analysis

274

SCX fractions were used for LC-MS/MS analysis and loaded on a pre-column (20 mm  100 lm; 5 lm-C18). Reversed phase chromatography was performed using the Thermo EASY-nLC 1000 (Thermo Fisher Scientific, San Jose, CA, USA) with a binary buffer system consisting of 0.1% formic acid (buffer A) and 84% ACN in 0.1% formic acid (buffer B). An analytical column (100 mm  75 lm; 3 lm-C18) was used. The online LC separation used a gradient from 0% to 35% buffer B for 100 min, then 35–100% buffer B for 8 min, and then 100% buffer B for 12 min. The flow rate was 250 nl/min. The column was operated at a constant temperature of 35 °C regulated by an in-house designed oven with a Peltier element. Peptides eluted from LC were directly injected into the coupled Q-Exactive mass spectrometer (Thermo Fisher Scientific) via the nanoelectrospray source (Thermo Fisher Scientific). A full MS scan was operated in the data-dependent mode and acquired over the range m/z 300–1800 with a mass resolution of 70,000 at m/z 200. Up to the top ten most abundant isotope patterns with a charge of P2 from the survey scan were selected with an isolation window of 1.6 Th and fragmented by higher energy collisional dissociation (HCD) with normalized collision energies of 25. The maximum ion injection times for the survey scan and the MS/MS scans were 20 and 60 ms, respectively, and the ion target value for both scan modes was set to 106. In this mode of operation, MS/MS scans were acquired with a mass resolution of 17,500 at m/z 200 and an isolation window of 2 m/z. Furthermore, since virtually all scans ‘‘time out’’ at 60 ms due to the high target value, the maximum ion signal in the fragmentation spectra is obtained.

275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306

307

Data analysis

308

Mascot 2.2 (Matrix Science, Boston, MA, USA) and Proteome Discoverer 1.3 (Thermo Fisher Scientific) software were used to simultaneously identify and quantify proteins based on the UniProt_Rat release 2013_03 database of 41,766 protein sequences. To calculate the false discovery rate (FDR) of peptide identification, the search was performed using the ‘‘decoy’’ option in Mascot. The user-defined search parameters were as follows: sample type as iTRAQ 8-plex (peptide-labeled), enzyme as trypsin, selection only of tryptic peptides with two missed cleavages, variable modifications of methionine oxidation, fixed modification of carbamidomethyl cysteine, peptide mass tolerance of ±20 ppm, and fragment mass tolerance of 0.1 Da. Proteome Discoverer 1.3 software was used to extract the peak intensity of each expected iTRAQ reporter ion from each analyzed fragmentation spectrum. The search parameters were as follows: peptide FDR <1%, the use of only unique peptides, rejection of all quantification values if not all quantification channels are present, normalization on protein median, normalization all peptide ratios by the median protein ratio, and median protein ratio = 1 after normalization. The relative quantity of a peptide among the different samples was

309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331

determined by comparing the intensities of reporter ion signals also present in the MS/MS scan. The results were then exported into Microsoft Excel for manual data interpretation. To minimize false positive results, a strict cutoff for protein identification was applied with FDR <1% as listed in Appendix Table 2. The resulting data set was autobias-corrected to eliminate any variations imparted due to unequal mixing of the different labeled samples. This correction is based on the assumption that the expression of most proteins did not change. This bias correction mitigates the systematic error arising from samples from each experimental condition that were not combined in exactly equal amounts. The software identified the median average protein ratio and corrected it to unity and then applied this factor to all quantification results. Proteins were considered for quantification if at least two unique peptides had a confidence interval of P95%. The proteins for further analysis were filtered with a p-value of less than 0.05 and 1.2-fold changes (>1.20 or <0.83) relative to control as shown in Appendix Table 3 (Ren et al., 2013).

332

Bioinformatics analysis

353

The theoretical molecular weight (MW) and isoelectric point (pI) of the identified proteins were retrieved from Mascot output files. The mapping of putative transmembrane domains (TMDs) for identified proteins was carried out using the TMHMM 2.0 program based on the transmembrane hidden Markov model (http:// www.cbs.dtu.dk/services/TMHMM) by submitting the FASTA files (Krogh et al., 2001). The grand average hydropathicity (GRAVY) values for identified proteins were analyzed using the ProtParam tool (available at http://web.expasy.org/protparam) (Zhou et al., 2008). The subcellular location (especially membrane association) and function of the identified differential proteins were elucidated by the gene ontology (GO) component and functional terms, respectively. The GO annotation associated with a given gene list was obtained using the Universal Protein Resource (UniProt) (http://www.uniprot.org) and the Database for Annotation, Visualization and Integrated Discovery (DAVID) 6.7 Bioinformatics tool (http://david.abcc.ncifcrf.gov) (Huang da et al., 2009). Then, the more detailed description of these differential membrane proteins with regard to synaptic components was derived from SynaptomeDB (http://psychiatry.igm. jhmi.edu/SynaptomeDB/) (Pirooznia et al., 2012).

354

RESULTS

378

333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352

355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377

CMS model and sucrose preference and behavioral assessment

379

The CMS rat model employed here is one of the most widely-used animal models for inducing depression-like behavior. In this study, sucrose preference was applied to assess CMS-induced anhedonic-like (susceptible) and CMS-resilient (unsusceptible) behavior of rats. After a four-week exposure to CMS, the stressed rats showing a <10% decrease in sucrose preference were regarded as being unsusceptible. The stressed rats were sorted into

381

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

380

382 383 384 385 386 387 388

NSC 16186

No. of Pages 73

22 April 2015

X. Han et al. / Neuroscience xxx (2015) xxx–xxx 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412

413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447

5

susceptible and unsusceptible groups based on a median split of their sucrose preference (median = 82.0%) with the susceptible group being defined as rats exhibiting a sucrose preference below the median. Subsequent ANOVA analysis showed that the sucrose preference of the susceptible group was significantly decreased when compared to the control and unsusceptible groups (F(2, 18) = 56.423, p < 0.001, Fig. 1A). The sucrose measurement indicated that rats exposed to CMS could be segregated into susceptible and unsusceptible populations. This segregation was further confirmed by subsequent behavioral testing. As assessed by the FST, the susceptible rats spent more time immobile compared with the control and unsusceptible groups (F(2, 18) = 19.692; p < 0.001), indicating that they developed a despair-like behavior by the end of the CMS exposure (Fig. 1B). There was no significant difference in either SPT (p = 0.895) or FST (p = 0.53) between the control and unsusceptible groups. Taken together, the anhedonia as SPT in susceptible rats was accompanied by increased immobility in the FST. The CMS paradigm described here offers a testable preclinical model that may be helpful in defining some stress-induced molecular aspects of MDD.

iTRAQ-based quantitative proteomic analysis of hippocampal PSD To study the effect of CMS on the expression of hippocampal PSD-associated proteins, a PSD-enriched subfraction was prepared by a combination of subcellular fractionation and Triton solubilization as described previously. Next, we used differential isotopic labeling with the iTRAQ reagent to quantitate differences in protein levels by tandem high-resolution mass spectrometry (Zhan et al., 2014). An overview of the iTRAQ experimental design and workflow conducted is shown in Fig. 2. PSD proteins from the control and stress animals were labeled using iTRAQ reagents, and then the labeled peptides were subjected to SCX fractionation and quantitatively profiled by LC-MS/MS using QExactive mass spectrometer. The expression level changes of proteins were indicated by the ratios of labeling tags (control: 115/118; susceptible: 113/116; unsusceptible: 114/117). The acquired MS/MS spectra were analyzed by database searching and stringent data filtering. In both the control and CMS conditions, a total of 1531 proteins were identified and quantitated with at least one unique peptide and 1% FDR (see Appendix Table 2). Among them, 558 were identified by a single peptide and not analyzed further. The remaining 973 (64%) proteins with two or more unique peptides (95% confidence) were selected for further analysis. The change in relative concentration of any given protein for susceptible and unsusceptible groups compared to the controls was obtained from iTRAQ 8-plex reporter ion ratios by a weighted average of all confidently identified peptides assigned to any given protein. iTRAQ reporter ratios of 1.2 and 0.83 were set as the cut-off value for protein changes. A total of 113 significantly altered proteins hits (either down- or up-regulated) were found responsive to CMS, all of which had at

Fig. 1. Sucrose preference and forced swim testing. Four-week exposure to CMS resulted in a significantly decreased sucrose preference and increased immobility time in susceptible rats when compared to control and unsusceptible rats (n = 7, ⁄p < 0.001).

least one ratio with a p-value <0.05 (Ren et al., 2013) (Appendix Table 3).

448

Identity categorization of differential proteins

450

The accession numbers of the 113 differential proteins identified from both the susceptible and unsusceptible groups were uploaded into the UniProt and DAVID databases for categorization of subcellular localization based on their GO annotations. In terms of cellular compartmentalization, 74 (65%) of the commonly differential proteins were initially defined as membraneassociated components (Fig. 3, left). Of these membrane proteins, 24 contained one or more TMDs predicted by TMHMM, and 14 exhibited a positive GRAVY value that was recognized as a relatively hydrophobic marker. To further investigate their relationship to the PSD, the detailed subtype localization of 74 differential membrane proteins were further investigated through an integrated database called SynaptomeDB (Pirooznia et al., 2012). SynaptomeDB compiled the synaptic protein list from a review of all peer-reviewed proteomics studies, as well from as publicly available databases that included proteins in the post-synapse, the pre-synapse, the presynaptic active zone, and the synaptic vesicle, and provided a detailed and experimentally verified annotation of all known synaptic proteins. Of these membrane proteins, 52 (70%) were identified by the SynaptomeDB search as having a predicted synapse-specific localization (see Appendix Table 3). As shown in Fig. 3 (right), 12, 11, 5, and 51

451

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

449

452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475

NSC 16186

No. of Pages 73

22 April 2015

6

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Fig. 2. Sample preparation and iTRAQ labeling for examining PSD proteomic changes. Hippocampal PSD fractions from the three experimental groups (control, susceptible, and unsusceptible) were prepared through a biochemical fractionation approach and subjected to 8-plex iTRAQ. Peptides from the control group were labeled with iTRAQ reagents having 115 and 118 reporters, peptides from the susceptible group were labeled with the iTRAQ reagent having 113 and 116 reporters, and peptides from the unsusceptible group were labeled with the iTRAQ reagent having 114 and 117 reporters. After labeling, peptides from all six samples were separately combined and fractionated by strong cation exchange (SCX) chromatography. Each fraction was then analyzed by LC-MS/MS by a Q-exactive mass spectrometer.

476 477 478 479 480 481 482

proteins were compartmentalized to the presynapse, presynaptic active zone, synaptic vesicle, and PSD, respectively. A four-way Venn diagram approach was used to display the overlap between these categories, and multiple overlapping sets were found. Not surprisingly, the vast majority of the 52 proteins were associated with PSD. It should be noted that the subcellular localization of 36

proteins was distinct from PSD. At the same time, we also observed that some postsynaptic proteins were simultaneously found in other regions, suggesting that they remain associated with these regions due to multiple localization.

483

Functional classification and disease relevance of differential PSD proteins

487

We applied iTRAQ technology to profile the hippocampal PSD proteome of a rodent depressive model in order to identify postsynaptic proteins specific to depression as well as increase our understanding of the signaling events underlying the pathology of MDD. Of the 51 PSD-associated proteins found, 37 were up-regulated and 14 were down-regulated in both susceptible and unsusceptible groups as compared to controls (Table 1). The results, analyzed as Venn diagrams (Fig. 4A), revealed that the susceptible phenotype was far more closely associated with the distinct up-regulation of protein groups at the hippocampal PSD. Among the 37 PSD-associated proteins found in the susceptible group, nine had similar changes to the unsusceptible group, while the remaining 28 proteins defined a unique phenotypic response to stress. To gain initial insights into the potential functions of these differential PSD-associated proteins, we classified each protein into both susceptible and unsusceptible groups into 10 different functional categories on the basis of their GO function annotations and literature surveys (Ashburner et al., 2000), though this classification could not be strict due to the multiple functions of a protein (Zhou et al., 2010) (Fig. 4B). The proteins were involved in an extensive set of synaptic functions, including signaling, regulatory, transporter, trafficking, etc. Notably, those proteins involved in trafficking were not found in the unsusceptible group. To further investigate the relationship between functional clusters and expressional alterations, the dysregulated phenotypes of these proteins in each category were systematically analyzed in the form of a heatmap. Fig. 4C displays a summary of altered proteins in each functional category, which emphasizes the unique dysregulations of protein expressions in the hippocampal PSD of susceptible or unsusceptible groups. A larger group of proteins were significantly changed in susceptible rats when compared to unsusceptible rats,

489

Fig. 3. Ontology analysis of differentially expressed proteins. (A) Pie chart showing the distribution of differentially expressed proteins by cellular components, which summarizes the percentages of membrane, non-membrane, and unknown proteins. Cellular location was determined by GO annotations from UniProt/DAVID database. (B) Venn diagram showing the detailed synaptic localization of all differential membrane-associated proteins based upon the above prediction and their overlap in terms of synaptome categories including presynaptic proteins, presynaptic active zone, synaptic vesicles, and postsynaptic density by SynaptomeDB search. Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

484 485 486

488

490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525

NSC 16186

No. of Pages 73

22 April 2015

7

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Table 1. Hippocampal PSD-associated proteins perturbed by CMS. Summary table showing significantly upregulated (") or downregulated (;) proteins found in the susceptible and unsusceptible groups relative to the control Accession number

Protein name

Gene name

% Sequence coverage

Susceptible

Unsusceptible

Function

3

16.7

"

M

Transporter

2 2

1.8 2.8

" "

M M

Trafficking Signaling

2 7

15.7 21.5

" "

M M

Regulatory Regulatory

2 6

6.9 6.4

" "

M M

Transporter Regulatory

2 3 4 3

3.3 15.1 20.1 5.6

" ; ; "

M M M M

Ppp1ca

4

13.3

;

M

Transporter Signaling Metabolic Cell adhesion Signaling

Gng3

2

3.2

"

M

Signaling

Erc2 Anxa6 Gpx4 Vamp2 Dlgap2 Slc25a11

4 2 2 3 2 2

6.5 2.2 13.0 35.3 2.8 8.0

" ; " " " "

M M M M M M

Nrgn Gdap1

3 5

26.9 14.0

" "

M M

Regulatory Transporter Metabolic Trafficking Signaling Receptor/ Carrier Signaling Other

Ppib Dnm1 l Tppp Ndufa7 Rtn3 Copa Nipsnap1

4 4 3 8 6 2 5

18.98 7.1 15.6 52.7 10.6 2.4 17.6

; " " " " " "

M M M M M M M

Other Regulatory Regulatory Metabolic Trafficking Transporter Trafficking

12

18.8

M

"

Metabolic

2

10.2

M

;

Camk2 g

8

16.7

M

"

Cell adhesion Signaling

Ak1 Prdx1 Rab12 Grm5

5 8 2 2

32.0 34.7 21.4 1.6

M M M M

" " ; "

Atp5 h Atp6v1b2

8 13

44.7 29.9

M M

" "

Cntnap1

2

3.1

M

;

Add3

2

4.8

M

;

Proteins differentially expressed only in the susceptible group G3V7Y3_RAT ATP synthase subunit delta, Atp5d mitochondrial UN13A_RAT Isoform 3 of Protein unc-13 homolog A Unc13a CNKR2_RAT Connector enhancer of kinase Cnksr2 suppressor of ras 2 D3ZT16_RAT Protein Map6d1 Map6d1 PACN1_RAT Protein kinase C and casein kinase Pacsin1 substrate in neurons protein 1 Q99P36_RAT Protein Syt7 Syt7 LRRC7_RAT Isoform 5 of Leucine-rich repeatLrrc7 containing protein 7 B5DEG8_RAT LOC685144 protein Sec24c B0BNK1_RAT Protein Rab5c Rab5c Q7TP78_RAT Aa2-258 Ndufa8 CADH2_RAT Cadherin-2 Cdh2 PP1A_RAT G3V8K2_RAT D3ZMM4_RAT ANXA6_RAT Q76LU9_RAT VAMP2_RAT DLGP2_RAT M2OM_RAT NEUG_RAT D4A5X7_RAT PPIB_RAT DNM1L_RAT D3ZQL7_RAT A9UMV9_RAT RTN3_RAT G3V6T1_RAT G3V728_RAT

Serine/threonine-protein phosphatase PP1-alpha catalytic subunit Guanine nucleotide-binding protein subunit gamma ERC protein 2 Annexin A6 Glutathione peroxidase Vesicle-associated membrane protein 2 Disks large-associated protein 2 Mitochondrial 2-oxoglutarate/malate carrier protein Neurogranin Ganglioside-induced differentiationassociated-protein 1 (Predicted) Peptidyl-prolyl cis–trans isomerase B Isoform 5 of Dynamin-1-like protein Protein Tppp Ndufa7 protein Reticulon-3 Protein Copa 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (C. elegans), isoform CRA_b

Proteins differentially expressed only in the unsusceptible group ODP2_RAT Dihydrolipoyllysine-residue Dlat acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial CD9_RAT CD9 antigen Cd9 F1LUE2_RAT KAD1_RAT PRDX1_RAT D4A376_RAT B2CZC8_RAT ATP5H_RAT VATB2_RAT CNTP1_RAT ADDG_RAT

Calcium/calmodulin-dependent protein kinase type II subunit gamma (Fragment) Adenylate kinase isoenzyme 1 Peroxiredoxin-1 Ras-related protein Rab-12 Glutamate receptor, metabotropic 5, isoform CRA_a ATP synthase subunit d, mitochondrial V-type proton ATPase subunit B, brain isoform Contactin-associated protein 1 (Fragment) Isoform 1 of Gamma-adducin

Unique peptides

Metabolic Regulatory Signaling Receptor/ Carrier Transporter Transporter Cell adhesion Cytoskeletal (continued on next page)

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

NSC 16186

No. of Pages 73

22 April 2015

8

X. Han et al. / Neuroscience xxx (2015) xxx–xxx Table 1 (continued) Accession number

Protein name

Gene name

Unique peptides

% Sequence coverage

Susceptible

Unsusceptible

Function

D3ZRF5_RAT

Protein Slc25a22

Slc25a22

10

34.1

M

"

AATM_RAT

Aspartate aminotransferase, mitochondrial Cytochrome c oxidase subunit 6B1

Got2

17

38.8

M

"

Receptor/ Carrier Metabolic

3

37.2

M

"

Metabolic

5.6 1.4 2.0

; ; ;

; ; ;

D3ZD09_RAT

Cox6b1

Proteins differentially expressed in both susceptible and unsusceptible groups DNJA2_RAT DnaJ homolog subfamily A member 2 Dnaja2 2 F1LSL8_RAT Protein Sptbn4 Sptbn4 3 NMDE1_RAT Glutamate receptor ionotropic, NMDA 2A Grin2a 2 G3V8C3_RAT CX7A2_RAT B1VKB4_RAT KCC2B_RAT VATE1_RAT Q91ZE7_RAT 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552

Vimentin Cytochrome c oxidase subunit 7A2, mitochondrial Synaptopodin Calcium/calmodulin-dependent protein kinase type II subunit beta V-type proton ATPase subunit E 1 Band 3 anion exchange protein

Vim Cox7a2

2 2

3.4 18.1

; ;

; ;

Chaperone Cytoskeletal Receptor/ Carrier Cytoskeletal Metabolic

Synpo Camk2b

3 15

7.6 31.9

" "

" "

Regulatory Signaling

Atp6v1e1 Slc4a1

7 3

22.6 4.8

" "

" "

Transporter Transporter

indicating that the progression of an anhedonic-like response to stress is more complex than a resilient response, and that the two stress phenotypes show differences in the abundance of several different types of proteins. Some protein systems, such as signaling and regulation, were markedly dysregulated in the susceptible group, implicating the association with significant depression-like behaviors. We also carried out a literature search to explore the relevance of the 51 differential PSD-associated proteins to mental illnesses. As shown in Fig. 5 and Appendix Table 4, many of these proteins have been reported in different disease states that can affect mood states such as depression, anxiety, schizophrenia, Alzheimer’s disease, and Huntington’s disease. Thirteen proteins have been found to be associated with depression, ten of which were altered in depressed human patients and eight of which were altered in animal models of depression. The dysregulation of these proteins was primarily in the hippocampus and prefrontal/frontal cortex. Furthermore, twenty-nine proteins have been implicated in four major mental illnesses (i.e., nine in anxiety, 15 in schizophrenia, 17 in Alzheimer’s disease, and eight in Huntington’s disease) with some proteins, such as Grin2a and Grm5, being related to multiple mood disorders (probably due to the diversity of their synaptic function).

553

DISCUSSION

554

A series of both preclinical and clinical studies has shown the hippocampal synapse to be affected in depressed subjects (Henningsen et al., 2012; Martins-de-Souza et al., 2012a,b; Duric et al., 2013; Martins-de-Souza, 2014). Although some nascent efforts have been made to investigate any potential molecular dysregulations to explain these effects (Duman, 2002, 2009), no direct causal relation has been established between these changes and depressed behavior (Martins-de-Souza et al., 2010;

555 556 557 558 559 560 561 562

Martins-de-Souza, 2014). Given this lack of knowledge on specific proteins and pathways associated with depression, novel molecular targets that may be involved in the pathogenesis of MDD are still being investigated. Our previous study carried out a two-dimensional gelelectrophoresis (2DE) proteomic analysis of hippocampal synaptosomal fractions and found 19 differential proteins in a CMS rodent model of depression (Hu et al., 2013). Generally, it is difficult to quantify global protein expression using the conventional 2DE technique because several proteins can migrate together and isoforms of the same protein can migrate to different places. Moreover, our previous results are somewhat biased toward abundant, soluble proteins, and only a small number of differential membrane proteins (particularly those with TMDs and high hydrophobicity) were detected. This type of protein is generally underrepresented in the 2DE, mainly due to their poor solubility in the starting buffer and protein aggregation during the isoelectric focusing step (Santoni et al., 2000a,b; Rabilloud, 2009; Zhou et al., 2010). Therefore, in order to discover lower abundance and more hydrophobic membrane proteins, herein we utilized a gel-free shotgun proteomic approach through combining PSD enrichment and FASP-based peptide preparation. In this approach, the PSD was enriched by common isolation methods (Phillips et al., 2001; AbulHusn et al., 2009; Focking et al., 2014), then a strong SDS extraction was used to maximize the solubility of the hydrophobic proteins (Wisniewski et al., 2009b; Zhou et al., 2010). Meanwhile, we took advantage of FASP-based direct digestion to efficiently remove the SDS (Wisniewski et al., 2009b), thereby improving the identification of highly hydrophobic membrane proteins as well as minimizing the experimental variance (Wisniewski et al., 2009a). The resulting tryptic peptides were labeled using iTRAQ reagents for MS-based quantitative analysis. CMS is considered one of the more valid rodent models of depression. By exposing rats to the CMS

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

563 564 565 566 567 568 569 570 571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594 595 596 597 598 599 600 601

NSC 16186

No. of Pages 73

22 April 2015

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

9

Fig. 4. Differential expression analysis of hippocampal PSD-associated proteins. (A) Venn diagrams showing the number of uniquely-regulated proteins in susceptible and unsusceptible groups as compared to controls with the overlap depicting proteins that were identically regulated by both conditions. Upregulated (red) and downregulated (green) proteins are shown separately. (B) Pie chart showing the classification of these differential PSD-associated proteins identified from susceptible and unsusceptible groups. The number of proteins in each category is indicated. (C) Up- or down-regulated proteins are indicated by red and green hues, respectively. The color intensity indicates the protein expressional level as displayed (top right). Histograms denote the expression trend of representative proteins. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616

regime, we selected rat groups with different stress response phenotypes through decreased sucrose preference and increased immobility, which provides evidence of depression-like status. A graded effect of stress exposure is expected, and a distinction into susceptible and unsusceptible rats provides a useful approach for identifying potential biomarkers specific for anhedonia as opposed to general stress-related effects. The resulting hippocampal PSD proteome was analyzed by quantitative proteomics, and numerous differential proteins from the two different CMS-response phenotypes were identified. Our investigation’s purpose was to focus on the analysis of hippocampal PSD protein changes in the rodent depression model. Initial differential data were

screened out by a SynaptomeDB search. A total of 52 proteins were found to be relevant to synapses, of which 51 were defined as PSD-associated proteins. Our purification method is enriched with respect to histologically-confirmed PSD proteins and has been shown to be valid for the PSD in rodents and post-mortem human brain tissue (Phillips et al., 2001; Abul-Husn et al., 2009; Focking et al., 2014). However, there are some proteins co-isolated that are known to be presynaptic or mitochondrial in origin. These proteins might be tightly bound to the PSD component and were therefore co-purified with the PSD (Peng et al., 2004; Yoshimura et al., 2004). But, this does not indicate that these proteins are unimportant or non-functional in synapses or in MDD development. Indeed, dendritic

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

617 618 619 620 621 622 623 624 625 626 627 628 629 630 631

NSC 16186

No. of Pages 73

22 April 2015

10

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Fig. 5. Differentially expressed PSD-associated proteins related to mental disorders. The associations between the differentially expressed proteins and mental disorders, such as depression, anxiety, Alzheimer’s disease, schizophrenia, and Huntington’s disease. Detailed protein descriptions and related literature have been summarized in Appendix Table 4.

632 633 634 635 636 637 638 639 640 641 642 643 644 645 646 647 648 649 650 651 652 653 654 655 656 657 658 659 660 661 662 663 664 665 666 667 668 669

mitochondria have been reported to contribute to neuron morphogenesis and synaptic plasticity (Li et al., 2004), and mitochondrial dysfunction may play an important role in MDD and other psychiatric disorders (Lin and Beal, 2006; Rezin et al., 2009). Here, both susceptible and unsusceptible rats were analyzed in order to discover several PSD-associated protein groups specifically related to CMS susceptibility. There were similar abundance changes between these two subgroups, and there was not a single protein whose abundance was changed in opposite directions in these two subgroups. These overlapping proteins in the two groups may only be as a result of exposure to stress, and while those altered differentially may mediate differences in behavior. More importantly, our proteomic data revealed a significant number of proteins that show changes in levels that are only specific to either susceptible or unsusceptible groups, suggesting differences in the stress response mechanism in these two phenotypes. Further functional analysis of PSDassociated proteins indicated that, in terms of protein expression levels in the hippocampal PSD microdomain, the susceptible group had a distinct proteome profile. In susceptible rats, some biological processes were heavily affected by CMS, such as signaling and regulation. Notably, these processes have been previously implicated in both stress responses and in MDD (Kinnunen et al., 2003; Carboni et al., 2006; Mu et al., 2007; Kang et al., 2012). Recent studies have found that CMS can induce depression-like behaviors in rats and increase glutamate concentration in the hippocampus (Lou et al., 2010). In general, the postsynaptic membrane in the brain’s excitatory synapses is specialized for responding rapidly to glutamate released from the presynaptic terminal. The postsynaptic membrane is associated with the PSD, which contains a high concentration of glutamate receptors and an ordered array of signaling, regulatory, and

cytoskeletal proteins. To some extent, excessive levels of excitatory amino acids – such as glutamate – could lead to the down-regulation of N-methyl-D-aspartate (NMDA) receptor subunits. In the present study, levels of the NMDA receptor subunit NR2A (Grin2a) and CamKIIbeta (Camk2b, as a potential calcium signal) were similarly changed in the two groups compared to the control group, suggesting CMS-induced dysfunction of the glutaminergic system in the hippocampus. However, the differential expression of many NMDA receptor downstream targets involved in glutamate signaling (Sanhueza and Lisman, 2013) were distinctly affected in susceptible rats, such as densin-180 (Lrrc7), protein kinases (Pacsin1, Nrgn), a small GTPase (Rab5c), and a G-protein (Gng3). Densin-180 is sufficiently abundant in the PSD (Apperson et al., 1996) and has been reported to bind directly to CaMKII and regulate both NMDA receptor-dependent and metabotropic glutamate receptor-dependent long-term depression (Quitsch et al., 2005). In susceptible rats, the up-regulation of densin-180 suggests that the alteration of long-term potentiation (which is generally dependent on NMDA receptor function) is critical to synaptic plasticity. Notably, densin180 was also found to be associated with other mental illnesses including schizophrenia and autism (Carlisle et al., 2011). Nrgn (neurogranin) is a neuron-specific postsynaptic protein. As a Ca2+-sensitive calmodulin (CaM) reservoir and a protein kinase C (PKC) substrate, Nrgn regulates the availability of calmodulin in axons and dendritic spines (Kubota et al., 2007; Zhong et al., 2009; DiezGuerra, 2010). Nrgn plays an important role in synaptic plasticity, learning, and memory and has been found to be related to spatial learning tasks with anxiety-related components (Miyakawa et al., 2001; Wilcoxon et al., 2007). Taken together, alterations of these key proteins involved in signal transduction and regulation appear to result in specific dysregulation in processes underlying synaptic plasticity (i.e., endocytosis, long-term potentiation, and calcium signaling) in susceptible rats. As the present analysis was restricted to the hippocampus, depression-specific alterations of PSD-associated proteins occurring in other brain regions (such as the prefrontal cortex and amygdala) require further investigation in future studies.

670

CONCLUSION

714

In conclusion, we used a broad discovery approach to profile the effects of CMS on the PSD-enriched proteome isolated from the rat hippocampus. The unbiased profiles identified several protein changes within the PSD that may be related to stress vulnerability or insusceptibility. Proteomic analysis supports the importance of the PSD in the pathogenesis of stress-related disorders and, in particular, points to a role for PSD-associated proteins involved in signaling and regulation. Taken together, these findings provide novel insights into the PSD’s contribution to stress susceptibility and mechanisms underlying NMDA receptor function and long-term potentiation that are responsible for this contribution.

715

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

671 672 673 674 675 676 677 678 679 680 681 682 683 684 685 686 687 688 689 690 691 692 693 694 695 696 697 698 699 700 701 702 703 704 705 706 707 708 709 710 711 712 713

716 717 718 719 720 721 722 723 724 725 726 727 728

NSC 16186

No. of Pages 73

22 April 2015

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

739

Acknowledgments—We thank Dr. Chenrui Hou (Shanghai Institute for Biological Sciences, Chinese Academy of Sciences) for his assistance with the mass spectrometric analysis. We thank the scientific editors at Impactys (www.impactys.com) for editing and proofreading this manuscript. This work was supported by grants from the National Basic Research Program of China (‘‘973 program’’, Grant No. 2009CB918300), the National Natural Science Foundation of China (Grant No. 81101009), and the Fund for Outstanding Young Scholars in the Chongqing Medical University (Grant No. 4101070036).

740

REFERENCES

741 742 743 744 745 746 747 748 749 750 751 752 753 754 755 756 757 758 759 760 761 762 763 764 765 766 767 768 769 770 771 772 773 774 775 776 777 778 779 780 781 782 783 784 785 786 787 788 789 790 791 792 793 794

Abul-Husn NS, Bushlin I, Moron JA, Jenkins SL, Dolios G, Wang R, Iyengar R, Ma’ayan A, Devi LA (2009) Systems approach to explore components and interactions in the presynapse. Proteomics 9:3303–3315. Apperson ML, Moon IS, Kennedy MB (1996) Characterization of densin-180, a new brain-specific synaptic protein of the Osialoglycoprotein family. J Neurosci 16:6839–6852. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25–29. Barabassy A, Beinhoff U, Riepe MW (2010) Cognitive estimation in aged patients with major depressive disorder. Psychiatry Res 176:26–29. Boyle LL, Porsteinsson AP, Cui X, King DA, Lyness JM (2010) Depression predicts cognitive disorders in older primary care patients. J Clin Psychiatry 71:74–79. Carboni L, Piubelli C, Pozzato C, Astner H, Arban R, Righetti PG, Hamdan M, Domenici E (2006) Proteomic analysis of rat hippocampus after repeated psychosocial stress. Neuroscience 137:1237–1246. Carlisle HJ, Luong TN, Medina-Marino A, Schenker L, Khorosheva E, Indersmitten T, Gunapala KM, Steele AD, O’Dell TJ, Patterson PH, Kennedy MB (2011) Deletion of densin-180 results in abnormal behaviors associated with mental illness and reduces mGluR5 and DISC1 in the postsynaptic density fraction. J Neurosci 31:16194–16207. Choudary PV, Molnar M, Evans SJ, Tomita H, Li JZ, Vawter MP, Myers RM, Bunney Jr WE, Akil H, Watson SJ, Jones EG (2005) Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc Natl Acad Sci U S A 102:15653–15658. Czeh B, Lucassen PJ (2007) What causes the hippocampal volume decrease in depression? Are neurogenesis, glial changes and apoptosis implicated? Eur Arch Psychiatry Clin Neurosci 257:250–260. D’Sa C, Duman RS (2002) Antidepressants and neuroplasticity. Bipolar Disord 4:183–194. Diez-Guerra FJ (2010) Neurogranin, a link between calcium/calmodulin and protein kinase C signaling in synaptic plasticity. IUBMB Life 62:597–606. Duman RS (2002) Structural alterations in depression: cellular mechanisms underlying pathology and treatment of mood disorders. CNS Spectr 7(140–142):144–147. Duman RS (2009) Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression. Dialogues Clin Neurosci 11:239–255. Duric V, Banasr M, Stockmeier CA, Simen AA, Newton SS, Overholser JC, Jurjus GJ, Dieter L, Duman RS (2013) Altered expression of synapse and glutamate related genes in postmortem hippocampus of depressed subjects. Int J Neuropsychopharmacol 16:69–82.

729 730 731 732 733 734 735 736 737 738

11

Focking M, Lopez LM, English JA, Dicker P, Wolff A, Brindley E, Wynne K, Cagney G, Cotter DR (2014) Proteomic and genomic evidence implicates the postsynaptic density in schizophrenia. Mol Psychiatry. Henningsen K, Palmfeldt J, Christiansen S, Baiges I, Bak S, Jensen ON, Gregersen N, Wiborg O (2012) Candidate hippocampal biomarkers of susceptibility and resilience to stress in a rat model of depression. Mol Cell Proteomics 11. M111.016428. Hu Y, Zhou J, Fang L, Liu H, Zhan Q, Luo D, Zhou C, Chen J, Li Q, Xie P (2013) Hippocampal synaptic dysregulation of exo/ endocytosis-associated proteins induced in a chronic mildstressed rat model. Neuroscience 230:1–12. Huang da W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57. Jay TM, Rocher C, Hotte M, Naudon L, Gurden H, Spedding M (2004) Plasticity at hippocampal to prefrontal cortex synapses is impaired by loss of dopamine and stress: importance for psychiatric diseases. Neurotox Res 6:233–244. Kang HJ, Voleti B, Hajszan T, Rajkowska G, Stockmeier CA, Licznerski P, Lepack A, Majik MS, Jeong LS, Banasr M, Son H, Duman RS (2012) Decreased expression of synapse-related genes and loss of synapses in major depressive disorder. Nat Med 18:1413–1417. Kinnunen AK, Koenig JI, Bilbe G (2003) Repeated variable prenatal stress alters pre- and postsynaptic gene expression in the rat frontal pole. J Neurochem 86:736–748. Klempan TA, Sequeira A, Canetti L, Lalovic A, Ernst C, ffrenchMullen J, Turecki G (2009) Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression. Mol Psychiatry 14:175–189. Krogh A, Larsson B, von Heijne G, Sonnhammer EL (2001) Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305:567–580. Kubota Y, Putkey JA, Waxham MN (2007) Neurogranin controls the spatiotemporal pattern of postsynaptic Ca2+/CaM signaling. Biophys J 93:3848–3859. Lecrubier Y (2001) The burden of depression and anxiety in general medicine. J Clin Psychiatry 62(Suppl. 8):4–9. discussion 10–11. Levens SM, Gotlib IH (2009) Impaired selection of relevant positive information in depression. Depress Anxiety 26:403–410. Li Z, Okamoto K, Hayashi Y, Sheng M (2004) The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119:873–887. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795. Liu RJ, Aghajanian GK (2008) Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: role of corticosterone-mediated apical dendritic atrophy. Proc Natl Acad Sci U S A 105:359–364. Lorenzetti V, Allen NB, Fornito A, Yucel M (2009) Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies. J Affect Disord 117:1–17. Lou JS, Li CY, Yang XC, Fang J, Yang YX, Guo JY (2010) Protective effect of gan mai da zao decoction in unpredictable chronic mild stress-induced behavioral and biochemical alterations. Pharm Biol 48:1328–1336. Martins-de-Souza D (2014) Proteomics, metabolomics, and protein interactomics in the characterization of the molecular features of major depressive disorder. Dialogues Clin Neurosci 16:63–73. Martins-de-Souza D, Guest PC, Harris LW, Vanattou-Saifoudine N, Webster MJ, Rahmoune H, Bahn S (2012a) Identification of proteomic signatures associated with depression and psychotic depression in post-mortem brains from major depression patients. Transl Psychiatry 2:e87. Martins-de-Souza D, Guest PC, Vanattou-Saifoudine N, Rahmoune H, Bahn S (2012b) Phosphoproteomic differences in major depressive disorder postmortem brains indicate effects on

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

795 796 797 798 799 800 801 802 803 804 805 806 807 808 809 810 811 812 813 814 815 816 817 818 819 820 821 822 823 824 825 826 827 828 829 830 831 832 833 834 835 836 837 838 839 840 841 842 843 844 845 846 847 848 849 850 851 852 853 854 855 856 857 858 859 860 861 862 863 864

NSC 16186

No. of Pages 73

22 April 2015

12 865 866 867 868 869 870 871 872 873 874 875 876 877 878 879 880 881 882 883 884 885 886 887 888 889 890 891 892 893 894 895 896 897 898 899 900 901 902 903 904 905 906 907 908 909 910 911 912 913 914 915 916 917 918 919 920

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

synaptic function. Eur Arch Psychiatry Clin Neurosci 262:657–666. Martins-de-Souza D, Harris LW, Guest PC, Turck CW, Bahn S (2010) The role of proteomics in depression research. Eur Arch Psychiatry Clin Neurosci 260:499–506. Miyakawa T, Yared E, Pak JH, Huang FL, Huang KP, Crawley JN (2001) Neurogranin null mutant mice display performance deficits on spatial learning tasks with anxiety related components. Hippocampus 11:763–775. Mu J, Xie P, Yang ZS, Yang DL, Lv FJ, Luo TY, Li Y (2007) Neurogenesis and major depression: implications from proteomic analyses of hippocampal proteins in a rat depression model. Neurosci Lett 416:252–256. Peng J, Kim MJ, Cheng D, Duong DM, Gygi SP, Sheng M (2004) Semiquantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spectrometry. J Biol Chem 279:21003–21011. Phillips GR, Huang JK, Wang Y, Tanaka H, Shapiro L, Zhang W, Shan WS, Arndt K, Frank M, Gordon RE, Gawinowicz MA, Zhao Y, Colman DR (2001) The presynaptic particle web: ultrastructure, composition, dissolution, and reconstitution. Neuron 32:63–77. Pirooznia M, Wang T, Avramopoulos D, Valle D, Thomas G, Huganir RL, Goes FS, Potash JB, Zandi PP (2012) SynaptomeDB: an ontology-based knowledgebase for synaptic genes. Bioinformatics 28:897–899. Pittenger C, Duman RS (2008) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33:88–109. Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732. Quitsch A, Berhorster K, Liew CW, Richter D, Kreienkamp HJ (2005) Postsynaptic shank antagonizes dendrite branching induced by the leucine-rich repeat protein Densin-180. J Neurosci 25:479–487. Rabilloud T (2009) Membrane proteins and proteomics: love is possible, but so difficult. Electrophoresis 30(Suppl. 1):S174–180. Radley JJ, Rocher AB, Miller M, Janssen WG, Liston C, Hof PR, McEwen BS, Morrison JH (2006) Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. Cereb Cortex 16:313–320. Ren Y, Hao P, Dutta B, Cheow ES, Sim KH, Gan CS, Lim SK, Sze SK (2013) Hypoxia modulates A431 cellular pathways association to tumor radioresistance and enhanced migration revealed by comprehensive proteomic and functional studies. Mol Cell Proteomics 12:485–498. Rezin GT, Amboni G, Zugno AI, Quevedo J, Streck EL (2009) Mitochondrial dysfunction and psychiatric disorders. Neurochem Res 34:1021–1029. Sanhueza M, Lisman J (2013) The CaMKII/NMDAR complex as a molecular memory. Mol Brain 6:10. Santoni V, Kieffer S, Desclaux D, Masson F, Rabilloud T (2000a) Membrane proteomics: use of additive main effects with multiplicative interaction model to classify plasma membrane proteins according to their solubility and electrophoretic properties. Electrophoresis 21:3329–3344.

Santoni V, Molloy M, Rabilloud T (2000b) Membrane proteins and proteomics: un amour impossible? Electrophoresis 21:1054–1070. Sequeira A, Klempan T, Canetti L, ffrench-Mullen J, Benkelfat C, Rouleau GA, Turecki G (2007) Patterns of gene expression in the limbic system of suicides with and without major depression. Mol Psychiatry 12:640–655. Sequeira A, Mamdani F, Ernst C, Vawter MP, Bunney WE, Lebel V, Rehal S, Klempan T, Gratton A, Benkelfat C, Rouleau GA, Mechawar N, Turecki G (2009) Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression. PLoS One 4:e6585. Sheline YI, Gado MH, Kraemer HC (2003) Untreated depression and hippocampal volume loss. Am J Psychiatry 160:1516–1518. Wilcoxon JS, Nadolski GJ, Samarut J, Chassande O, Redei EE (2007) Behavioral inhibition and impaired spatial learning and memory in hypothyroid mice lacking thyroid hormone receptor alpha. Behav Brain Res 177:109–116. Wisniewski JR, Zougman A, Mann M (2009a) Combination of FASP and StageTip-based fractionation allows in-depth analysis of the hippocampal membrane proteome. J Proteome Res 8:5674–5678. Wisniewski JR, Zougman A, Nagaraj N, Mann M (2009b) Universal sample preparation method for proteome analysis. Nat Methods 6:359–362. Yang Y, Yang D, Tang G, Zhou C, Cheng K, Zhou J, Wu B, Peng Y, Liu C, Zhan Y, Chen J, Chen G, Xie P (2013) Proteomics reveals energy and glutathione metabolic dysregulation in the prefrontal cortex of a rat model of depression. Neuroscience 247:191–200. Yoshimura Y, Yamauchi Y, Shinkawa T, Taoka M, Donai H, Takahashi N, Isobe T, Yamauchi T (2004) Molecular constituents of the postsynaptic density fraction revealed by proteomic analysis using multidimensional liquid chromatographytandem mass spectrometry. J Neurochem 88:759–768. Zhan Y, Yang YT, You HM, Cao D, Liu CY, Zhou CJ, Wang ZY, Bai SJ, Mu J, Wu B, Zhan QL, Xie P (2014) Plasma-based proteomics reveals lipid metabolic and immunoregulatory dysregulation in post-stroke depression. Eur Psychiatry 29:307–315. Zhong L, Cherry T, Bies CE, Florence MA, Gerges NZ (2009) Neurogranin enhances synaptic strength through its interaction with calmodulin. EMBO J 28:3027–3039. Zhou J, Li J, Li J, Chen P, Wang X, Liang S (2010) Dried polyacrylamide gel absorption: a method for efficient elimination of the interferences from SDS-solubilized protein samples in mass spectrometry-based proteome analysis. Electrophoresis 31:3816–3822. Zhou J, Lin Y, Deng X, Shen J, He Q, Chen P, Wang X, Liang S (2008) Development and application of a two-phase, onmembrane digestion method in the analysis of membrane proteome. J Proteome Res 7:1778–1783.

921 922 923 924 925 926 927 928 929 930 931 932 933 934 935 936 937 938 939 940 941 942 943 944 945 946 947 948 949 950 951 952 953 954 955 956 957 958 959 960 961 962 963 964 965 966 967 968 969 970

APPENDIX

971 972

Appendix Table 1. Time and length of stressors used in the CMS procedure

Paired housing Cage tilt 45° Soiled cage Water deprivation Empty water bottle Strobe light Continuous lighting White noise

Sunday

Monday

?

10:00 13:00–19:00

18:00

?

10:00 10:00–11:00

13:00–18:00 18:00

?

10:00

Tuesday

Wednesday

Thursday

Friday

Saturday

21:00

17:00

12:00

?

19:00

?

12:00

19:00

?

12:00 12:00–15:00

18:00-20:00

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

Unique peptides

Ratio

p-Value

Ratio

p-Value

Ratio

p-Value

Ratio

p-Value

Q2TVU3_RAT

TID1 OS = Rattus norvegicus GN = Dnaja3 PE = 2 SV = 1 Protein Dnajb14 OS = Rattus norvegicus GN = Dnajb14 PE = 4 SV = 1 Sn1-specific diacylglycerol lipase alpha OS = Rattus norvegicus GN = Dagla PE = 2 SV = 1 Calcium-binding protein 4 (Fragment) OS = Rattus norvegicus GN = Hsp90b1 PE = 1 SV = 1 Synapsin-3 OS = Rattus norvegicus GN = Syn3 PE = 1 SV = 1 Protein Fam40a OS = Rattus norvegicus GN = Fam40a PE = 4 SV = 1 Synaptopodin OS = Rattus norvegicus GN = Synpo PE = 2 SV = 1 Protein Rab6b (Fragment) OS = Rattus norvegicus GN = Rab6b PE = 3 SV = 1 Protein Epm2aip1 (Fragment) OS = Rattus norvegicus GN = Epm2aip1 PE = 4 SV = 1 Malonyl-CoA decarboxylase, mitochondrial OS = Rattus norvegicus GN = Mlycd PE = 2 SV = 1 Splicing factor proline/glutamine rich (Polypyrimidine tract binding protein associated) OS = Rattus norvegicus GN = Sfpq PE = 2 SV = 1 FAS-associated factor 2 OS = Rattus norvegicus GN = Faf2 PE = 2 SV = 1 Protein LOC362419 OS = Rattus norvegicus GN = Tamm41 PE = 4 SV = 1 Protein RGD1562402 OS = Rattus norvegicus GN = RGD1562402 PE = 3 SV = 1 Probable lysosomal cobalamin transporter OS = Rattus norvegicus GN = Lmbrd1 PE = 2 SV = 1 Rps16 protein (Fragment) OS = Rattus norvegicus GN = Rps16 PE = 2 SV = 1 Protein IMPACT OS = Rattus norvegicus GN = Impact PE = 2 SV = 1 Uncharacterized protein OS = Rattus norvegicus GN = Rpl26-ps1 PE = 3 SV = 1

1

1

3.5

49411.56

9.41

0

0.435

8.85655

4.71E89

2.73994

2.35E15

5.94148

8.76E42

1.44815

0.107306

1

1

4.2

42346.12

8.83

0

0.762

7.17252

1.34E55

0.83651

0.384806

5.32796

2.19E32

1.60146

0.030475

2

2

3.5

6

5

0.077

3.60509

4.14E11

3.86442

6.96E39

1.26976

0.521404

0.666667

0.132887

1

1

100.0

1977.99

3.8

0

1.239

4.93312

1.69E23

0.71722

0.133523

4.70244

4.46E24

0.630599

0.096027

1

1

4.2

63347.91

9.47

0

0.531

2.45201

0.000257

3.42466

2.45E28

5.9807

1.99E42

3.10362

3.28E14

1

1

2.5

95608.78

5.83

0

0.395

2.80513

5.20E06

2.36942

4.55E10

1.86153

0.022881

0.985606

0.941235

4

3

7.6

96717.32

9.69

0

0.711

3.47943

3.43E10

2.04391

2.02E06

3.96524

6.21E16

1.49719

0.073864

1

1

7.5

21067.66

5.18

0

0.462

3.72706

4.83E12

1.73373

0.000842

2.0798

0.003999

1.12458

0.658271

1

1

3.7

52757.04

5.51

0

0.151

1.93157

0.020023

1.96824

1.05E05

2.09538

0.003487

1.08546

0.763344

1

1

2.6

54761.41

8.96

0

0.225

3.51253

1.98E10

1.14455

0.512449

2.90003

2.70E07

1.07967

0.779328

1

1

1.4

75485.88

9.45

0

1.13

3.34636

2.88E09

1.12399

0.574536

3.97971

4.47E16

1.27139

0.330903

1

1

5.5

41079.08

5.71

0

0.739

3.04

2.52E07

1.20504

0.352086

3.14699

5.70E09

1.19112

0.494914

1

1

6.5

37785.35

9.06

0

0.14

1.33426

0.423253

2.77315

6.87E16

0.876574

0.616899

0.571385

0.053638

1

1

8.1

16587.22

10.99

0

0.599

2.80205

5.40E06

1.30913

0.16013

3.43551

3.54E11

1.3329

0.232333

1

1

3.4

61017.62

7.87

9

0.374

2.09364

0.006149

1.83561

0.000143

4.39788

1.70E20

2.13751

4.15E05

2

2

13.2

17899.83

10.21

0

0.342

3.11855

8.48E08

1.22029

0.317311

2.41858

0.000137

1.14013

0.618171

3

2

7.6

35994.52

5.07

0

0.593

2.35611

0.00065

1.5469

0.012861

1.82125

0.03045

0.924053

0.726697

1

1

4.8

17165

10.37

0

1.011

0.975207

0.880645

2.48618

1.33E11

1.33235

0.415614

1.02699

0.928285

D3ZPU2_RAT

DGLA_RAT

Q7M079_RAT

SYN3_RAT G3V8E2_RAT

B1VKB4_RAT F1LVC3_RAT

F1M471_RAT

DCMC_RAT

Q4KM71_RAT

FAF2_RAT D3ZKT0_RAT

D3ZF07_RAT

LMBD1_RAT

Q5XFV9_RAT

IMPCT_RAT

D4AE42_RAT

% Sequence coverage

MW (Da)

115300.1

pI

TMDs

GRAVY

Susceptible 113/115

Unsusceptible 114/ 115

Susceptible 116/118

Unsusceptible 117/ 118

(continued on next page)

13

No. of Pages 73

Peptides

NSC 16186

Protein description

22 April 2015

Accession number

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

Appendix Table 2. A list of all identified and quantified proteins (1531 proteins) with at least one unique peptide (95% confidence) determined from the susceptible and unsusceptible groups. MW, molecular weight; pI, isoelectric point; TMDs, transmembrane domains; GRAVY, grand average hydropathicity

Q6RKB3_RAT

THOC1_RAT

B1H271_RAT

D3ZII1_RAT Q4V7D4_RAT

SKP1_RAT

DJB11_RAT

ERMIN_RAT VAMP2_RAT

PHYD1_RAT

Q6IMZ5_RAT

TSSC1_RAT

D3ZWL6_RAT

B2RZ27_RAT

F1LSR8_RAT

60822.84

7.24

2

0.142

1.30014

0.475429

1.88387

5.76E05

4.32687

1.05E19

1.47305

0.089076

1

1

1.6

85964.97

8.5

0

0.572

2.84222

3.30E06

1.15806

0.473653

2.14129

0.002304

0.821632

0.418834

1

1

2.6

93303.75

8.54

8

0.144

1.29891

0.477372

1.14792

0.502613

1.9267

0.014072

0.956039

0.836636

1

1

2.0

93180.5

5.64

1

0.426

2.67256

2.47E05

0.641767

0.05748

1.45143

0.253083

0.396004

0.006616

1

1

2.0

75419.11

4.89

0

0.608

2.98959

4.97E07

0.860993

0.459597

2.78511

1.39E06

1.15112

0.590505

2

1

5.4

35185.3

9.86

1

0.054

2.57105

7.53E05

1.67045

0.002286

1.81188

0.032491

1.04947

0.864103

1

1

4.9

44851.74

5.65

0

0.746

2.11849

0.00506

0.847917

0.418683

1.38028

0.343934

0.620959

0.087707

2

2

8.5

54746.58

5.25

0

0.552

2.32033

0.000905

1.05318

0.811212

1.59251

0.125398

0.745962

0.251171

1

1

2.6

50824.28

7.63

0

0.292

2.23092

0.002

1.23344

0.289188

1.62719

0.103464

0.780583

0.321014

2

2

11.0

18671.82

4.4

0

0.716

2.32185

0.000892

1.36503

0.097071

1.99347

0.008296

1.19424

0.487824

1

1

4.8

40494.5

5.92

1

0.556

1.80835

0.044292

2.05251

1.66E06

1.26401

0.531773

1.32224

0.247726

1

1

6.7

32227.57

4.64

0

1.199

1.48112

0.239688

1.47877

0.029459

1.36696

0.363019

1.06691

0.814891

13

3

35.3

12690.64

7.84

1

0.004

2.18637

0.002916

1.26408

0.23036

1.47564

0.226375

0.900461

0.648942

1

1

4.8

34567.93

5.62

0

0.192

3.0144

3.57E07

1.35865

0.10306

1.10767

0.846517

0.665702

0.131776

1

1

4.7

40453.56

4.97

0

0.562

1.87652

0.028863

1.06334

0.77552

2.10193

0.003289

0.994964

0.974646

1

1

4.4

43156.4

4.9

0

0.425

1.83591

0.037372

1.04295

0.847509

1.98387

0.008968

0.992256

0.964968

1

1

4.1

56395.14

8.49

0

0.261

2.16324

0.003529

1.29745

0.176549

1.28191

0.499836

0.700463

0.176573

2

2

29.0

10476.63

5.02

0

0.522

2.12015

0.004994

0.879848

0.522351

2.37561

0.00022

0.861222

0.528005

3

2

32.0

8304.69

7.65

0

0.121

1.96822

0.015541

0.715778

0.131559

1.50322

0.198474

0.650938

0.115652

2

1

1.8

5.55

0

0.227

1.97583

0.01473

1.22106

0.315606

1.47817

0.223703

0.872279

0.560899

122164.9

No. of Pages 73

G3V8K2_RAT

4.0

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

D3ZJL5_RAT

2

NSC 16186

ABCB6_RAT

2

22 April 2015

D3ZGZ1_RAT

Cytochrome P450 4F4 OS = Rattus norvegicus GN = Cyp4f4 PE = 3 SV = 1 SH3-containing GRB2-like protein 3interacting protein 1 OS = Rattus norvegicus GN = Sgip1 PE = 2 SV = 1 ATP-binding cassette sub-family B member 6, mitochondrial OS = Rattus norvegicus GN = Abcb6 PE = 2 SV = 1 Fasciclin II transmembrane protein isoform OS = Rattus norvegicus GN = Ncam2 PE = 2 SV = 1 THO complex subunit 1 OS = Rattus norvegicus GN = Thoc1 PE = 2 SV = 1 Mitochondrial coenzyme A transporter SLC25A42 OS = Rattus norvegicus GN = Slc25a42 PE = 2 SV = 1 Uncharacterized protein OS = Rattus norvegicus PE = 4 SV = 1 Protein Rftn2 OS = Rattus norvegicus GN = Rftn2 PE = 4 SV = 1 Family with sequence similarity 126, member B OS = Rattus norvegicus GN = Fam126b PE = 2 SV = 1 S-phase kinase-associated protein 1 OS = Rattus norvegicus GN = Skp1 PE = 2 SV = 3 DnaJ homolog subfamily B member 11 OS = Rattus norvegicus GN = Dnajb11 PE = 2 SV = 1 Ermin OS = Rattus norvegicus GN = Ermn PE = 1 SV = 1 Vesicle-associated membrane protein 2 OS = Rattus norvegicus GN = Vamp2 PE = 1 SV = 2 Phytanoyl-CoA dioxygenase domaincontaining protein 1 (Fragment) OS = Rattus norvegicus GN = Phyhd1 PE = 2 SV = 1 Tropomodulin 1 OS = Rattus norvegicus GN = Tmod1 PE = 2 SV = 1 Protein TSSC1 OS = Rattus norvegicus GN = Tssc1 PE = 2 SV = 1 Adenosylhomocysteinase OS = Rattus norvegicus GN = Ahcyl2 PE = 2 SV = 1 Protein Sh3bgrl3 OS = Rattus norvegicus GN = Sh3bgrl3 PE = 4 SV = 1 Guanine nucleotide-binding protein subunit gamma OS = Rattus norvegicus GN = Gng3 PE = 3 SV = 1 Voltage-dependent calcium channel subunit alpha-2/delta-3 OS = Rattus norvegicus GN = Cacna2d3 PE = 2 SV = 1

14

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

CP4F4_RAT

TRXR2_RAT

PSA1_RAT

INP4B_RAT

D3ZT16_RAT

RASA3_RAT

F1MAH8_RAT D4A4F9_RAT

Q498C9_RAT NSF1C_RAT

F1LRA1_RAT

ARP2_RAT RL3_RAT G3V7H5_RAT

F1M084_RAT

CADM2_RAT

G3V7I3_RAT

HD_RAT MT3_RAT

13.0

29111.31

10.31

0

0.875

2.07201

0.007263

1.22491

0.307243

1.97087

0.009955

0.930798

0.7495

1

1

4.9

34048.49

6.59

0

0.056

2.29508

0.001138

1.60191

0.006179

1.11139

0.838471

0.860438

0.525712

1

1

4.7

45625.51

7.11

0

0.322

1.7687

0.056126

2.55022

1.70E12

1.95547

0.011249

2.73394

4.05E10

1

1

2.5

56424.14

8.82

0

0.112

2.40491

0.000408

1.3145

0.152981

1.44394

0.261768

1.00692

0.986005

1

1

7.6

29517.18

6.14

0

0.431

2.43401

0.000308

1.06923

0.755046

1.23881

0.578401

0.622141

0.088695

1

1

1.4

5.69

0

0.349

2.39871

0.000434

1.51367

0.019478

1.57203

0.139956

0.992241

0.964917

3

2

15.7

20412.55

9.94

0

0.516

1.84475

0.035356

1.27709

0.20814

1.67856

0.076706

1.0115

0.972804

2

2

4.4

96016.32

7.25

0

0.448

1.76814

0.056309

1.18363

0.40484

1.11332

0.834317

0.655559

0.120522

1

1

1.2

5.24

0

0.824

1.80089

0.046344

1.4772

0.029998

1.08215

0.902041

0.730694

0.224015

1

1

9.2

15018.64

6.7

1

0.916

1.50073

0.220252

0.873242

0.499876

2.19778

0.001355

0.8625

0.531757

1

1

2.6

52778.28

9.2

0

0.649

1.57734

0.155183

1.08967

0.685412

1.49444

0.20707

0.727066

0.217883

2

2

9.2

40679.45

5.04

0

0.638

1.77483

0.054139

1.07763

0.726166

1.621

0.107141

0.724476

0.213579

1

1

3.9

57819.18

5.68

1

0.544

1.68408

0.090265

1.12778

0.562815

1.23221

0.590934

0.691296

0.163785

6

3

15.7

32490.99

6.15

0

0.123

2.04618

0.00883

1.13564

0.538932

1.79542

0.036362

0.945658

0.800489

1

1

2.7

46135.41

10.22

0

0.645

1.74559

0.064161

1.09027

0.683425

1.91923

0.014901

0.824801

0.427051

1

1

1.7

56937.79

9.08

0

0.312

2.03132

0.009862

1.06264

0.777972

1.85439

0.024089

0.833457

0.449971

1

1

1.3

5.88

0

0.59

1.16813

0.706462

1.14931

0.498576

1.57908

0.134806

0.925822

0.732655

4

3

15.1

5.13

0

0.216

1.79388

0.04834

1.08379

0.705208

1.19242

0.66894

0.601753

0.072865

1

1

1.4

8.37

0

0.11

1.48434

0.236417

0.925753

0.691514

1.72741

0.056774

0.977157

0.911163

1

1

3.2

4.52

0

0.985

2.01362

0.011231

1.52063

0.017888

1.95133

0.011622

1.31478

0.25893

1

1

0.5

5.91

0

0.065

1.3652

0.378974

1.65521

0.002874

1.67731

0.077279

1.23543

0.39952

1

1

19.7

8.04

0

0.458

1.78583

0.050725

0.843035

0.403976

2.07143

0.004302

0.866048

0.542241

106484.1

148277

124392.1

39608.36

131914

27682.86

343758 6809.04

15

(continued on next page)

No. of Pages 73

PAGR1_RAT

2

NSC 16186

PRS8_RAT

3

22 April 2015

TM40L_RAT

Glutathione peroxidase OS = Rattus norvegicus GN = Gpx4 PE = 2 SV = 2 Mitochondrial import receptor subunit TOM40B OS = Rattus norvegicus GN = Tomm40l PE = 1 SV = 1 26S protease regulatory subunit 8 OS = Rattus norvegicus GN = Psmc5 PE = 1 SV = 1 Thioredoxin reductase 2, mitochondrial OS = Rattus norvegicus GN = Txnrd2 PE = 1 SV = 3 Proteasome subunit alpha type-1 OS = Rattus norvegicus GN = Psma1 PE = 1 SV = 2 Isoform 2 of Type II inositol 3,4bisphosphate 4-phosphatase OS = Rattus norvegicus GN = Inpp4b Protein Map6d1 OS = Rattus norvegicus GN = Map6d1 PE = 4 SV = 1 Ras GTPase-activating protein 3 OS = Rattus norvegicus GN = Rasa3 PE = 2 SV = 1 Protein Clip1 OS = Rattus norvegicus GN = Clip1 PE = 2 SV = 1 Protein LOC682489 OS = Rattus norvegicus GN = LOC682489 PE = 4 SV = 1 Protein Zfp207 OS = Rattus norvegicus GN = Zfp207 PE = 4 SV = 1 NSFL1 cofactor p47 OS = Rattus norvegicus GN = Nsfl1c PE = 1 SV = 1 Protein ERGIC-53 OS = Rattus norvegicus GN = Lman1 PE = 2 SV = 1 Actin-related protein 2 OS = Rattus norvegicus GN = Actr2 PE = 2 SV = 1 60S ribosomal protein L3 OS = Rattus norvegicus GN = Rpl3 PE = 1 SV = 3 E74-like factor 2, isoform CRA_b OS = Rattus norvegicus GN = Elf2 PE = 3 SV = 1 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (Fragment) OS = Rattus norvegicus GN = Plcb1 PE = 2 SV = 1 Cell adhesion molecule 2 (Fragment) OS = Rattus norvegicus GN = Cadm2 PE = 2 SV = 1 ATPase type 13A1 (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Atp13a1 PE = 3 SV = 1 PAXIP1-associated glutamate-rich protein 1 OS = Rattus norvegicus GN = PAGR1 PE = 2 SV = 2 Huntingtin OS = Rattus norvegicus GN = Htt PE = 1 SV = 1 Metallothionein-3 OS = Rattus norvegicus GN = Mt3 PE = 2 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

Q76LU9_RAT

G3V7Y3_RAT

GATA_RAT

G3V8U9_RAT

D3ZHL1_RAT ARF5_RAT

D3Z8X1_RAT Q91ZE7_RAT

B2LYI9_RAT

UN13A_RAT STMN1_RAT PPM1F_RAT CNKR2_RAT RTN3_RAT A1E5S7_RAT DLGP2_RAT SHAN3_RAT SRBS2_RAT B2GUZ3_RAT F1M5F9_RAT F1M5B8_RAT

TXNL1_RAT D3ZQL7_RAT D4AD48_RAT

1.86981

0.030141

0.97524

0.892677

1.40174

0.314568

0.820801

0.416693

6.41

0

0.949

1.97706

0.014603

1.26546

0.227926

1.26531

0.52941

0.855664

0.511851

6.01

0

0.647

1.8738

0.029374

0.756778

0.1967

1.37116

0.356938

0.659188

0.124459

17562.79

5.16

0

0.211

1.81525

0.042467

1.18238

0.408058

2.16807

0.001796

1.18527

0.508343

3.4

56837.03

5.61

0

0.086

2.06135

0.007877

2.22253

2.62E08

0.693767

0.285413

0.700628

0.17681

1

5.7

29228.03

5.65

0

0.161

2.15818

0.003678

1.5844

0.007852

1.59085

0.126531

1.29446

0.291159

1

1

1.7

96731.86

8.88

0

0.526

1.76505

0.057335

1.24511

0.265681

1.27536

0.511396

0.82771

0.434678

1

1

5.6

20529.42

6.3

0

0.204

1.80781

0.044438

1.14613

0.507817

1.76742

0.043848

1.26353

0.345203

1

1

2.6

77920.02

4.34

0

0.844

1.65748

0.103934

1.25961

0.238359

4.54038

3.91E22

3.29302

1.33E16

5

4

6.5

6

6

6.4

10

3

16.7

1

1

1

134457.2

98023.61 158648.5

1

1

4.1

27354.92

9.92

0

0.537

2.01764

0.010906

1.63513

0.003859

1.42953

0.279063

1.16594

0.554097

5

3

4.8

94311.68

5.83

10

0.327

1.43918

0.28521

2.31773

1.99E09

2.38937

0.000189

3.28321

1.79E16

1

1

1.0

4.79

0

1.76939

0.055897

0.871478

0.493962

1.09017

0.884529

0.521787

0.031398

Isoform 3 of Protein unc-13 homolog A OS = Rattus norvegicus GN = Unc13a Stathmin OS = Rattus norvegicus GN = Stmn1 PE = 1 SV = 2 Protein phosphatase 1F OS = Rattus norvegicus GN = Ppm1f PE = 2 SV = 1 Connector enhancer of kinase suppressor of ras 2 OS = Rattus norvegicus GN = Cnksr2 PE = 2 SV = 1 Reticulon-3 OS = Rattus norvegicus GN = Rtn3 PE = 1 SV = 1 Nel-like 2 splice variant OS = Rattus norvegicus GN = Nell2 PE = 2 SV = 1 Disks large-associated protein 2 OS = Rattus norvegicus GN = Dlgap2 PE = 1 SV = 3 Isoform 1 of SH3 and multiple ankyrin repeat domains protein 3 OS = Rattus norvegicus GN = Shank3 Sorbin and SH3 domain-containing protein 2 OS = Rattus norvegicus GN = Sorbs2 PE = 1 SV = 2 Mthfd1l protein OS = Rattus norvegicus GN = Mthfd1l PE = 2 SV = 1 Protein Efr3b (Fragment) OS = Rattus norvegicus GN = Efr3b PE = 2 SV = 1 Protein Astn1 (Fragment) OS = Rattus norvegicus GN = Astn1 PE = 4 SV = 1 Cadherin-2 OS = Rattus norvegicus GN = Cdh2 PE = 1 SV = 1 Dihydropyrimidinase-related protein 4 OS = Rattus norvegicus GN = Dpysl4 PE = 2 SV = 1 Thioredoxin-like protein 1 OS = Rattus norvegicus GN = Txnl1 PE = 2 SV = 1 Protein Tppp OS = Rattus norvegicus GN = Tppp PE = 4 SV = 1 Protein Dcun1d2 OS = Rattus norvegicus GN = Dcun1d2 PE = 4 SV = 1

221416

0.41

5.15

0

0.554

1.81562

0.042369

1.28698

0.192316

2.07493

0.004173

1.05959

0.835476

5.76 5.19

0 0

1.313 0.22

2.00308 1.02976

0.012124 0.981407

1.07894 1.59773

0.7217 0.006545

1.91688 2.04845

0.01517 0.005245

1.06063 1.31689

0.832535 0.255723

109695.9

6.09

0

0.776

1.82396

0.040251

0.722787

0.141321

1.49871

0.202854

0.680763

0.149966

10.6 2.5

101515.7 86433.29

5 5.48

3 0

0.409 0.38

1.56595 1.62766

0.163808 0.121157

1.21607 1.04999

0.32671 0.82249

1.89721 1.07486

0.017599 0.918004

0.970207 0.670958

0.886517 0.137919

2

2.8

118977.2

6.3

0

0.868

2.28604

0.001234

1.21635

0.326083

1.33779

0.407061

0.67704

0.1453

4

4

3.4

192384.5

9

0

0.57

1.63122

0.11899

1.03526

0.875052

1.63912

0.096667

0.969209

0.882985

1

1

1.5

134055.9

8.7

0

0.869

1.62436

0.12319

1.19641

0.372799

1.91145

0.015809

0.848395

0.491119

2

2

2.6

105840.9

7.29

0

0.092

1.67336

0.095587

1.42632

0.052575

2.27685

0.000621

1.41568

0.135387

2

2

3.8

6.39

0

0.175

1.95817

0.016673

1.12943

0.55776

1.28001

0.503185

0.750393

0.259466

5

3

4.0

5.25

0

0.331

2.4942

0.000168

0.851422

0.429436

1.56489

0.145331

1.09681

0.732311

6 3

3 3

5.6 6.3

99685.04 64173.55

4.61 6.58

1 0

0.347 0.176

1.90336 1.72952

0.024202 0.07029

1.14542 1.03332

0.509898 0.882011

1.60723 1.46078

0.115683 0.242516

0.902012 0.849002

0.65395 0.492835

3

3

13.9

33600.59

4.81

0

0.293

1.70413

0.08095

1.17343

0.43154

1.19978

0.654202

0.790155

0.342372

9 1

3 1

15.6 6.6

23546.3 29999.76

9.45 5.39

0 0

0.748 0.51

1.75205 1.6502

0.061826 0.107944

1.20499 1.10267

0.35222 0.642434

1.84113 1.25126

0.02648 0.555122

1.09131 0.765088

0.747308 0.288322

3

2

1.8

2 1

2 1

16.1 3.3

5

2

2.8

7 1

6 1

3

194360.9 17288.28 49164.92

87513.01 135268.2

No. of Pages 73

CADH2_RAT DPYL4_RAT

0.461

1.1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

PJA2_RAT

0

1

NSC 16186

LRRC7_RAT

8.3

1

22 April 2015

D3ZMM4_RAT

Probable G-protein coupled receptor 158 OS = Rattus norvegicus GN = Gpr158 PE = 3 SV = 1 ERC protein 2 OS = Rattus norvegicus GN = Erc2 PE = 4 SV = 1 Isoform 5 of Leucine-rich repeatcontaining protein 7 OS = Rattus norvegicus GN = Lrrc7 ATP synthase subunit delta, mitochondrial OS = Rattus norvegicus GN = Atp5d PE = 3 SV = 1 Glutamyl-tRNA(Gln) amidotransferase subunit A, mitochondrial OS = Rattus norvegicus GN = Qrsl1 PE = 2 SV = 1 Proteasome subunit beta type OS = Rattus norvegicus GN = Psmb4 PE = 3 SV = 1 Protein Ksr1 OS = Rattus norvegicus GN = Ksr1 PE = 2 SV = 1 ADP-ribosylation factor 5 OS = Rattus norvegicus GN = Arf5 PE = 1 SV = 2 E3 ubiquitin-protein ligase Praja-2 OS = Rattus norvegicus GN = Pja2 PE = 2 SV = 1 Uncharacterized protein OS = Rattus norvegicus PE = 4 SV = 1 Band 3 anion exchange protein OS = Rattus norvegicus GN = Slc4a1 PE = 2 SV = 1 Tenascin C OS = Rattus norvegicus GN = Tnc PE = 2 SV = 1

16

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

GP158_RAT

F1M281_RAT Q99P36_RAT F1LP46_RAT LRC8C_RAT Q6IRL2_RAT D4ADS9_RAT D4A0V6_RAT ECI1_RAT PDE2A_RAT BCAS1_RAT D4A1Q9_RAT PACN1_RAT NCKX2_RAT B5DEG8_RAT D4ABB2_RAT

Q9ES33_RAT F1LZ81_RAT D3ZNY3_RAT

D4A9Z6_RAT P5I11_RAT CYLD_RAT CX6C2_RAT G3V728_RAT

D3ZSN7_RAT

ROGDI_RAT CH037_RAT SCFD1_RAT

Sec1 family domain-containing protein 1 OS = Rattus norvegicus GN = Scfd1 PE = 2 SV = 1

1

3.4

2

2

2.8

1

1

1.9

1

1

2 1

8.91

0

0.419

1.7416

0.065641

1.07982

0.718686

1.45309

0.251183

0.881428

0.588842

6.29

0

0.919

1.6873

0.088712

0.853568

0.436097

1.54261

0.163108

0.686789

0.157759

93726.48

8.32

0

0.151

2.5354

0.00011

2.13699

2.28E07

0.776896

0.417967

1.02049

0.946955

2.0

97013.02

6.3

0

0.176

1.0531

0.933943

1.27577

0.210322

1.39711

0.320762

0.733833

0.22942

2 1

6.9 2.8

58160.81 77826.52

9.35 6.7

1 0

0.532 0.277

1.86126 1.80117

0.031841 0.046264

1.03799 0.884369

0.865262 0.538023

1.46107 1.16362

0.242198 0.727792

0.944809 0.694991

0.797551 0.168854

1

1

2.0

92461.61

7.97

0

0.098

1.48343

0.237331

1.02343

0.917668

1.30435

0.46129

0.755454

0.26917

1 1

1 1

2.5 1.7

86179.92 92522.89

6.41 6.36

1 0

0.291 0.153

1.47726 1.74617

0.243647 0.063948

1.05333 1.52498

0.810664 0.016951

1.25845 1.3084

0.54188 0.454518

0.801189 1.30878

0.368094 0.268174

1 1

1 1

1.4 5.5

122559.9 32254.03

8.08 9.55

0 0

0.572 0.156

1.76994 1.55879

0.055717 0.169415

1.23914 1.21546

0.277538 0.328074

1.09198 1.01258

0.88058 0.938095

0.700717 0.739199

0.176939 0.238872

4

4

5.4

103262

5.24

0

0.202

1.66889

0.09788

1.06243

0.778701

1.15934

0.73667

0.774479

0.307857

4

4

10.0

63711.01

7.7

0

0.949

1.61726

0.127661

1.4599

0.036499

1.24658

0.56381

0.979225

0.918514

1

1

2.2

73897.12

5.39

0

0.396

0.492556

0.080909

1.07713

0.727873

2.00349

0.007643

0.461202

0.015374

9

7

21.5

50448.57

5.15

0

1.02

1.8529

0.033581

1.15996

0.468306

1.24948

0.558424

0.640845

0.105552

3

2

3.4

74655.81

5.93

11

0.209

1.62693

0.1216

0.930795

0.711296

2.10525

0.003193

0.988757

0.952479

2

2

3.3

6.71

0

0.228

1.88383

0.027522

1.10479

0.635558

1.74991

0.049162

1.1784

0.524372

1

1

4.7

44305.25

8.36

0

0.324

1.44628

0.277118

1.17155

0.436564

0.996406

0.898206

0.790703

0.343623

1 3

1 2

5.1 1.4

30762.82 225192.8

4.57 8.09

0 0

0.579 0.355

1.43235 1.4342

0.293143 0.290985

1.08292 1.31483

0.708164 0.152548

1.59021 1.14599

0.126972 0.764646

1.03616 0.742164

0.902014 0.244211

1

1

3.9

46329.24

9.64

0

0.209

1.8094

0.044012

1.09255

0.675799

1.14519

0.766322

0.916108

0.700147

2

1

5.9

36206.27

9.26

0

0.572

1.56707

0.162942

1.09888

0.654849

0.970649

0.835264

0.595434

0.068457

1

1

7.9

20938.52

9.43

4

0.341

1.45648

0.265773

1.20895

0.342945

1.26382

0.5321

0.845727

0.483625

2

2

2.9

5.44

0

0.354

1.7638

0.057754

1.05168

0.816491

2.0484

0.005246

1.24799

0.374631

10

2

27.6

10.07

1

0.108

1.7896

0.049595

0.980969

0.916695

1.94724

0.012

1.09994

0.723818

10

5

17.6

33345.9

9.44

0

0.596

1.63347

0.117636

1.17614

0.424343

2.07727

0.004089

1.38827

0.16324

1

1

4.8

37878.66

9.68

0

0.018

1.83193

0.038312

1.07859

0.722897

1.22658

0.601702

0.819609

0.413636

5

4

7.1

82538.89

6.51

0

0.266

1.69747

0.083952

1.24623

0.263505

1.79993

0.035264

1.37945

0.173072

1

1

7.3

32204.74

8.32

0

0.102

1.70329

0.081325

1.01697

0.941053

1.30611

0.458349

0.960696

0.852971

1

1

7.1

23770.5

6.44

0

0.728

1.32057

0.443768

1.01818

0.936673

1.0356

0.995106

0.624104

0.090355

1

2.6

79274.95 131355.7

118522.8

106711.4 8454.83

43970.84

5.72

0

0.728

1.57714

0.155334

1.07365

0.739818

1.69457

0.069622

1.15572

0.579081

17

(continued on next page)

No. of Pages 73

DNM1L_RAT

2

NSC 16186

G3V9J8_RAT

2

22 April 2015

Q3ZB99_RAT

Choline transporter-like protein 2 OS = Rattus norvegicus GN = Slc44a2 PE = 2 SV = 1 Tight junction protein 2 OS = Rattus norvegicus GN = Tjp2 PE = 2 SV = 1 Glycerol-3-phosphate acyltransferase 1, mitochondrial OS = Rattus norvegicus GN = Gpam PE = 4 SV = 1 Calcium-transporting ATPase type 2C member 1 (Fragment) OS = Rattus norvegicus GN = Atp2c1 PE = 2 SV = 1 Protein Syt7 OS = Rattus norvegicus GN = Syt7 PE = 2 SV = 1 ATP-dependent RNA helicase SUPV3L1, mitochondrial (Fragment) OS = Rattus norvegicus GN = Supv3l1 PE = 2 SV = 1 Leucine-rich repeat-containing protein 8C OS = Rattus norvegicus GN = Lrrc8c PE = 2 SV = 1 Mitofusin 2 OS = Rattus norvegicus GN = Mfn2 PE = 2 SV = 1 Protein Efr3a OS = Rattus norvegicus GN = Efr3a PE = 4 SV = 1 Protein Anln OS = Rattus norvegicus GN = Anln PE = 4 SV = 1 Enoyl-CoA delta isomerase 1, mitochondrial OS = Rattus norvegicus GN = Eci1 PE = 1 SV = 1 cGMP-dependent 3’,5’-cyclic phosphodiesterase (Fragment) OS = Rattus norvegicus GN = Pde2a PE = 2 SV = 1 Isoform 5 of Breast carcinoma-amplified sequence 1 homolog OS = Rattus norvegicus GN = Bcas1 Protein Ttll12 OS = Rattus norvegicus GN = Ttll12 PE = 4 SV = 1 Protein kinase C and casein kinase substrate in neurons protein 1 OS = Rattus norvegicus GN = Pacsin1 PE = 1 SV = 1 Sodium/potassium/calcium exchanger 2 OS = Rattus norvegicus GN = Slc24a2 PE = 2 SV = 1 LOC685144 protein OS = Rattus norvegicus GN = Sec24c PE = 2 SV = 1 Megalencephalic leukoencephalopathy with subcortical cysts 1 homolog (Human) (Predicted) OS = Rattus norvegicus GN = Mlc1 PE = 4 SV = 1 Protein Dkk3 OS = Rattus norvegicus GN = Dkk3 PE = 2 SV = 1 Protein Dock4 OS = Rattus norvegicus GN = Dock4 PE = 2 SV = 1 Methylmalonic aciduria (Cobalamin deficiency) cblA type (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Mmaa PE = 4 SV = 1 Mitochondrial ribosomal protein S35 (Predicted) OS = Rattus norvegicus GN = Mrps35 PE = 4 SV = 1 Tumor protein p53-inducible protein 11 OS = Rattus norvegicus GN = Tp53i11 PE = 2 SV = 1 Ubiquitin carboxyl-terminal hydrolase CYLD OS = Rattus norvegicus GN = Cyld PE = 2 SV = 1 CX6C2_RAT Cytochrome c oxidase subunit 6C-2 OS = Rattus norvegicus GN = Cox6c2 PE = 1 SV = 3 G3V728_RAT 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (C. elegans), isoform CRA_b OS = Rattus norvegicus GN = Nipsnap1 PE = 4 SV = 1 Protein Slc25a44 OS = Rattus norvegicus GN = Slc25a44 PE = 3 SV = 1 Isoform 5 of Dynamin-1-like protein OS = Rattus norvegicus GN = Dnm1l Protein rogdi homolog OS = Rattus norvegicus GN = Rogdi PE = 2 SV = 1 Protein C8orf37 homolog OS = Rattus norvegicus PE = 2 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

CTL2_RAT

D4A899_RAT CDK5_RAT NUCB2_RAT D4AEC2_RAT D3ZVA6_RAT CATA_RAT DLG3_RAT LRC8A_RAT OXR1_RAT PLRKT_RAT A9UMV9_RAT NB5R3_RAT UGGG1_RAT RIMB2_RAT CSPG2_RAT PCCA_RAT RAB6A_RAT PLCL1_RAT Q8CHN5_RAT HPLN2_RAT CSPG5_RAT PPT1_RAT NEGR1_RAT M2OM_RAT

HNRH1_RAT Q5RJN0_RAT

231808.5

5.37

0

0.142

1.69039

0.087245

0.95116

0.793054

1.07533

0.916974

0.666946

0.13321

1

1

7.1

30313.6

5.14

1

0.095

1.50921

0.212214

1.25391

0.248857

1.00096

0.909421

0.766518

0.291242

1

1

5.5

37915.92

5.69

0

0.368

1.46861

0.252694

1.07353

0.740207

2.45634

8.93E-05

1.41466

0.136353

11

3

8.7

27803.89

9.32

2

0.597

1.65754

0.103897

1.03291

0.883482

1.53044

0.173482

0.948695

0.811025

1

1

0.3

5.56

0

0.171

1.89316

0.02589

1.27983

0.203668

1.33913

0.404976

1.014

0.965607

347445.7

1

1

5.5

33254.06

7.57

0

0.298

1.58362

0.150577

0.940048

0.748097

1.46097

0.242309

0.736956

0.234887

1

1

3.1

50089.67

5.02

0

1.063

1.60425

0.13618

1.12006

0.586809

1.22089

0.612692

0.725228

0.214823

1

1

1.0

6.6

0

0.752

1.11746

0.804723

1.42615

0.052668

0.944691

0.772881

0.783869

0.328244

2

2

22.1

10214.47

5.57

0

0.681

1.47525

0.245724

1.11312

0.608727

1.34054

0.402779

0.758399

0.274929

1 6

1 5

3.0 8.9

59756.49 92171.01

7.07 6.39

0 0

0.639 0.501

1.30763 1.71541

0.463688 0.076064

1.34653 1.02292

0.11526 0.919521

1.08191 1.26638

0.902571 0.527484

1.06428 0.825948

0.822259 0.430049

1

1

2.2

94160.53

8.15

4

0.119

1.83012

0.038746

0.916497

0.655755

1.14783

0.760762

0.660882

0.12633

5

3

5.6

92808.97

5.01

0

0.703

1.5342

0.189752

1.18083

0.412052

1.22712

0.600668

0.754241

0.266822

4

1

6.8

17312.13

9.48

0

0.286

1.25101

0.556373

1.42072

0.05576

2.34975

0.00029

1.72628

0.008936

11

8

52.7

12500.31

10.48

0

0.662

1.66864

0.098011

1.0147

0.949279

1.84332

0.026072

0.853033

0.504295

2

2

9.5

34865.15

8.56

0

0.16

1.24571

0.565506

1.28882

0.189479

1.92744

0.013993

1.12624

0.653927

1

1

1.0

176428.5

5.43

0

0.317

1.66263

0.101166

1.20882

0.343259

0.969525

0.832538

0.848009

0.490031

1

1

1.6

115612.9

5.06

0

0.581

1.50928

0.212152

1.07588

0.732148

1.0876

0.890128

0.738086

0.236889

9

4

2.0

300004.3

4.49

0

0.551

1.46411

0.257493

0.859754

0.455628

1.39443

0.324381

0.735065

0.231566

4

4

7.3

81621.88

7.6

0

0.216

1.54909

0.177234

1.22819

0.300205

1.3667

0.363406

1.12155

0.666205

2

2

11.1

23589.51

5.42

0

0.416

1.60292

0.137077

1.02735

0.903531

1.59069

0.12664

1.0372

0.899058

1

1

1.3

5.47

0

0.341

0.886596

0.657743

2.37851

3.49E10

0.835177

0.529434

1.39156

0.159693

1

1

10.7

16363.87

7.55

0

0.038

0.817822

0.502635

1.33053

0.133072

0.910086

0.692012

0.697516

0.172384

11

6

20.5

38046.09

9.3

0

0.296

1.59861

0.140003

1.41672

0.058135

1.33494

0.411535

1.28439

0.308088

2

1

2.8

60957.89

4.41

2

0.449

1.84924

0.034369

1.07307

0.74179

1.33367

0.413534

0.839102

0.465288

3

2

11.8

31531.1

6.72

0

0.197

1.63154

0.118793

1.90674

3.68E05

0.947669

0.779973

1.54995

0.047937

1

1

3.7

37857.63

6.1

0

0.071

0.717555

0.31646

1.01929

0.932657

4.23923

9.43E19

3.85032

8.46E25

6

2

8.0

34132.51

9.89

0

0.101

1.42587

0.300805

1.09563

0.665571

1.74927

0.049367

1.12853

0.647992

4

3

26.9

7496.25

6.53

0

0.612

1.58853

0.147048

1.03698

0.868888

1.76185

0.045485

1.1586

0.571999

2

2

5.5

51218.21

6.21

0

0.564

1.55516

0.172309

0.926022

0.692565

1.41711

0.294586

0.919357

0.710963

7

3

22.5

23944.78

10.02

0

0.042

1.59913

0.139651

0.946884

0.775663

1.37804

0.347104

0.865329

0.540108

165610.2

122771.1

No. of Pages 73

NEUG_RAT

3.3

NSC 16186

PRIO_RAT

4

22 April 2015

CLVS2_RAT

5

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

ITM2B_RAT

Protein Plxnb1 OS = Rattus norvegicus GN = Plxnb1 PE = 4 SV = 1 Integral membrane protein 2B OS = Rattus norvegicus GN = Itm2b PE = 2 SV = 1 Clavesin-2 OS = Rattus norvegicus GN = Clvs2 PE = 1 SV = 1 Major prion protein OS = Rattus norvegicus GN = Prnp PE = 1 SV = 2 Protein Vps13a OS = Rattus norvegicus GN = Vps13a PE = 2 SV = 1 Cyclin-dependent kinase 5 OS = Rattus norvegicus GN = Cdk5 PE = 1 SV = 1 Nucleobindin-2 OS = Rattus norvegicus GN = Nucb2 PE = 2 SV = 1 Protein Camsap1l1 OS = Rattus norvegicus GN = Camsap2 PE = 4 SV = 1 Protein Bola2 OS = Rattus norvegicus GN = Bola2 PE = 3 SV = 1 Catalase OS = Rattus norvegicus GN = Cat PE = 1 SV = 3 Isoform Short of Disks large homolog 3 OS = Rattus norvegicus GN = Dlg3 Leucine-rich repeat-containing protein 8A OS = Rattus norvegicus GN = Lrrc8a PE = 2 SV = 1 Oxidation resistance protein 1 OS = Rattus norvegicus GN = Oxr1 PE = 1 SV = 3 Plasminogen receptor (KT) OS = Rattus norvegicus GN = Plgrkt PE = 1 SV = 1 Ndufa7 protein OS = Rattus norvegicus GN = Ndufa7 PE = 4 SV = 1 Isoform 2 of NADH-cytochrome b5 reductase 3 OS = Rattus norvegicus GN = Cyb5r3 UDP-glucose:glycoprotein glucosyltransferase 1 OS = Rattus norvegicus GN = Uggt1 PE = 1 SV = 2 RIMS-binding protein 2 OS = Rattus norvegicus GN = Rimbp2 PE = 1 SV = 2 Versican core protein (Fragments) OS = Rattus norvegicus GN = Vcan PE = 2 SV = 2 Propionyl-CoA carboxylase alpha chain, mitochondrial OS = Rattus norvegicus GN = Pcca PE = 1 SV = 3 Ras-related protein Rab-6A OS = Rattus norvegicus GN = Rab6a PE = 2 SV = 2 Inactive phospholipase C-like protein 1 OS = Rattus norvegicus GN = Plcl1 PE = 1 SV = 1 Epididymal secretory protein 1 OS = Rattus norvegicus GN = Npc2 PE = 2 SV = 1 Hyaluronan and proteoglycan link protein 2 OS = Rattus norvegicus GN = Hapln2 PE = 2 SV = 1 Chondroitin sulfate proteoglycan 5 OS = Rattus norvegicus GN = Cspg5 PE = 1 SV = 1 Palmitoyl-protein thioesterase 1 (Fragment) OS = Rattus norvegicus GN = Ppt1 PE = 4 SV = 1 Neuronal growth regulator 1 OS = Rattus norvegicus GN = Negr1 PE = 1 SV = 1 Mitochondrial 2-oxoglutarate/malate carrier protein OS = Rattus norvegicus GN = Slc25a11 PE = 2 SV = 3 Neurogranin OS = Rattus norvegicus GN = Nrgn PE = 1 SV = 1 Protein Hnrph1 OS = Rattus norvegicus GN = Hnrph1 PE = 2 SV = 1 NADH dehydrogenase (Ubiquinone) Fe-S protein 7 OS = Rattus norvegicus GN = Ndufs7 PE = 2 SV = 1

18

D3ZDX5_RAT

G3V982_RAT

KCNA6_RAT SCPDL_RAT GABT_RAT Q06QG6_RAT F1LPP6_RAT GDE1_RAT F1M787_RAT VATE1_RAT F1LNN7_RAT Q8R2H0_RAT DHSB_RAT

G3V6T1_RAT STXB5_RAT NFASC_RAT DCLK1_RAT D3ZNN0_RAT O35791_RAT B0BN83_RAT F1LSM3_RAT Q6IRH7_RAT ABLM2_RAT BAG5_RAT

F1LVV3_RAT F1LRK4_RAT

12.5

26377.12

5.02

0

2

2

15.7

11922.49

7.89

0

5

3

9.4

56468.48

6.94

2

2

4.4

82426.88

1

1

3.0

2

2

18

1.61308

0.130355

1.23777

0.280308

1.08782

0.889657

0.854257

0.507803

0.38

1.41737

0.311065

0.906068

0.616392

1.82527

0.029609

0.989835

0.956326

0

0.032

1.6109

0.131775

1.22083

0.316132

1.18859

0.676651

1.00323

0.996626

5.66

0

0.327

1.31261

0.455961

1.17671

0.422846

1.44829

0.256703

1.1127

0.689591

58883.22

5

4

0.082

1.42463

0.302293

0.903676

0.607511

1.27509

0.511883

1.14854

0.596948

9.9

35411.12

8.09

0

0.12

1.85696

0.032727

1.39332

0.07376

1.55531

0.152779

1.42393

0.127764

8

22.8

56455.15

8.15

0

0.285

1.67752

0.093494

1.46937

0.032803

1.07932

0.908233

1.01557

0.961099

7

3

7.9

68587.28

9.34

15

0.621

1.68515

0.089746

1.54435

0.013287

1.2839

0.496345

1.39349

0.157635

3

2

4.8

75970.73

4.73

0

0.688

1.68349

0.090553

1.16145

0.464166

0.934815

0.749505

0.721798

0.209195

1

1

4.5

37633.74

6.26

0

0.089

1.60357

0.136636

0.88088

0.525907

1.52989

0.173962

0.990551

0.958882

4

4

5.2

8.44

0

0.514

1.51666

0.205328

0.939742

0.746868

1.72244

0.058581

0.818361

0.41045

12

7

22.6

8.44

0

0.49

1.56403

0.165295

1.61803

0.00493

1.94464

0.012247

1.96348

0.000519

121665.4 26128.12

0.056

15

9

7.8

5.29

0

0.476

1.59294

0.143936

0.919224

0.666213

1.63022

0.101705

1.20059

0.473548

4

3

28.6

12164.29

5.84

0

0.938

1.51278

0.20889

1.00905

0.969781

1.04904

0.974739

0.676383

0.144489

5

5

18.1

31829.64

8.96

0

0.37

1.41043

0.319598

1.66788

0.002377

2.72809

3.03E06

3.20927

1.61E-15

2

2

2.4

138358.3

7.69

0

0.279

1.6798

0.092359

1.03846

0.863568

2.06645

0.004493

1.52781

0.057695

3

3

5.4

121741.4

6.46

0

0.289

1.65701

0.104187

1.07344

0.740529

1.01672

0.948317

0.801543

0.36894

34

15

18.0

138002.6

5.79

2

0.513

1.40231

0.329785

0.978168

0.904942

1.3026

0.464232

0.896419

0.63597

3

3

9.7

5.52

0

0.408

1.46234

0.259394

1.20543

0.351168

1.38168

0.34197

1.12843

0.64824

3

2

1.5

8.37

0

0.316

1.62372

0.123591

1.27744

0.207568

0.966773

0.825874

1.01211

0.971052

10

4

25.3

19686.18

4.89

0

0.475

1.46183

0.259945

1.0664

0.764863

1.44978

0.254983

0.947952

0.808443

3

2

5.3

31204.1

5.41

0

0.316

1.43645

0.288367

1.15136

0.492676

1.25835

0.542076

1.1866

0.505285

1

1

1.6

98996.55

5.53

0

0.67

1.82255

0.040603

1.69091

0.001669

0.889315

0.645041

0.687325

0.158467

1

1

2.4

75678.49

8.68

0

0.454

1.52123

0.201186

0.935377

0.729442

0.915226

0.703829

0.686575

0.157477

2

1

2.3

68552.57

8.36

0

0.549

1.4695

0.251755

1.17799

0.419478

1.16608

0.722689

0.778882

0.317311

2

1

4.5

51029.89

5.84

0

0.483

1.50338

0.21772

1.12089

0.584186

0.990875

0.884622

0.710837

0.191928

55

15

31.9

60401.11

6.73

0

0.353

1.73409

0.068502

1.34355

0.118429

1.83977

0.026737

1.56141

0.043456

1

1

2.5

70961.21

7.47

0

0.379

1.37857

0.360748

1.12111

0.5835

0.931139

0.740862

0.657919

0.123071

1

1

3.3

53200.94

6.9

0

0.42

1.51419

0.20759

1.15603

0.47937

1.42935

0.279294

1.03779

0.897351

135654.5

47680.29 175668.8

19

(continued on next page)

No. of Pages 73

KCC2B_RAT

2

NSC 16186

AL9A1_RAT

2

22 April 2015

FKB1A_RAT

Uncharacterized protein OS = Rattus norvegicus GN = Abca8a PE = 4 SV = 1 Peptidyl-prolyl cis-trans isomerase FKBP1A OS = Rattus norvegicus GN = Fkbp1a PE = 1 SV = 3 4-trimethylaminobutyraldehyde dehydrogenase OS = Rattus norvegicus GN = Aldh9a1 PE = 3 SV = 1 Engulfment and cell motility 2, ced-12 homolog (C. elegans), isoform CRA_c OS = Rattus norvegicus GN = Elmo2 PE = 4 SV = 1 Potassium voltage-gated channel subfamily A member 6 OS = Rattus norvegicus GN = Kcna6 PE = 2 SV = 1 Saccharopine dehydrogenase-like oxidoreductase OS = Rattus norvegicus GN = Sccpdh PE = 2 SV = 1 4-aminobutyrate aminotransferase, mitochondrial OS = Rattus norvegicus GN = Abat PE = 1 SV = 3 NADH-ubiquinone oxidoreductase chain 5 OS = Rattus norvegicus GN = Mt-nd5 PE = 3 SV = 1 A-kinase anchor protein 5 OS = Rattus norvegicus GN = Akap5 PE = 2 SV = 1 Glycerophosphodiester phosphodiesterase 1 OS = Rattus norvegicus GN = Gde1 PE = 1 SV = 2 Catenin delta-2 OS = Rattus norvegicus GN = Ctnnd2 PE = 2 SV = 1 V-type proton ATPase subunit E 1 OS = Rattus norvegicus GN = Atp6v1e1 PE = 1 SV = 1 Neurocan core protein OS = Rattus norvegicus GN = Ncan PE = 2 SV = 1 Protein Atp6v1g2 OS = Rattus norvegicus GN = Atp6v1g2 PE = 2 SV = 1 Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial OS = Rattus norvegicus GN = Sdhb PE = 2 SV = 2 Protein Copa OS = Rattus norvegicus GN = Copa PE = 4 SV = 1 Isoform 3 of Syntaxin-binding protein 5 OS = Rattus norvegicus GN = Stxbp5 Neurofascin OS = Rattus norvegicus GN = Nfasc PE = 1 SV = 2 Serine/threonine-protein kinase DCLK1 OS = Rattus norvegicus GN = Dclk1 PE = 2 SV = 1 Protein Sbf1 OS = Rattus norvegicus GN = Sbf1 PE = 4 SV = 1 RhoA (Fragment) OS = Rattus norvegicus GN = Rhoa PE = 2 SV = 1 Armadillo repeat-containing protein 1 OS = Rattus norvegicus GN = Armc1 PE = 2 SV = 1 WD repeat-containing protein 44 (Fragment) OS = Rattus norvegicus GN = Wdr44 PE = 2 SV = 1 ClpB caseinolytic peptidase B homolog (E. coli) OS = Rattus norvegicus GN = Clpb PE = 2 SV = 1 Actin-binding LIM protein 2 OS = Rattus norvegicus GN = Ablim2 PE = 2 SV = 1 BAG family molecular chaperone regulator 5 OS = Rattus norvegicus GN = Bag5 PE = 1 SV = 1 Calcium/calmodulin-dependent protein kinase type II subunit beta OS = Rattus norvegicus GN = Camk2b PE = 1 SV = 1 Uncharacterized protein (Fragment) OS = Rattus norvegicus PE = 4 SV = 1 Protein Grsf1 OS = Rattus norvegicus GN = Grsf1 PE = 2 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

D3ZCF8_RAT

D4A8U7_RAT UCRI_RAT RHOB_RAT CSTN1_RAT F1M2K6_RAT Q9JMB3_RAT ACTN4_RAT

A6Y857_RAT CR1L_RAT D3ZDT1_RAT F1M8K1_RAT F1M6N9_RAT PACS1_RAT SHAN2_RAT D4A435_RAT SNP25_RAT B0BNF6_RAT LPPRC_RAT NLGN2_RAT F1LV09_RAT NFL_RAT D4A6H8_RAT THTM_RAT

Q5BKB9_RAT D3ZXA6_RAT

65605.57

5.49

0

0.282

1.16902

0.704785

1.16745

0.447654

1.23264

0.590114

0.86266

0.532227

1

1

2.2

56916.08

5.84

0

0.509

1.38804

0.348192

1.1414

0.521719

1.5267

0.176769

0.993869

0.970732

1

1

2.5

50850.66

9.14

0

0.175

1.10297

0.833481

1.51549

0.01905

1.06798

0.933102

0.831009

0.443421

1

1

1.1

5.34

0

0.582

1.35026

0.399991

1.18782

0.394149

1.45986

0.243541

1.03912

0.893568

13

7

23.7

29445.36

9.04

0

0.108

1.41647

0.312156

1.0274

0.903327

1.67505

0.078331

1.11077

0.69472

11

4

25.0

22123.15

5.1

1

0.26

1.44313

0.280688

1.25113

0.254096

1.42578

0.283699

1.02277

0.940405

1

1

1.6

106259.7

4.91

1

0.427

1.57098

0.159953

1.48826

0.026384

1.31028

0.4514

1.35866

0.197977

3

3

3.9

127228.6

9.24

0

0.657

1.32541

0.436451

0.906027

0.616237

0.870811

0.60435

0.562313

0.048793

14

9

9.9

119689.6

5.04

0

0.677

1.51906

0.203139

0.963577

0.844113

1.17342

0.707567

0.834105

0.451714

8

6

7.0

104913.8

5.27

0

0.654

1.53778

0.186683

1.107

0.628387

1.1039

0.854674

0.837242

0.460211

3

2

22.6

11558.77

4.15

0

2.047

1.4956

0.22523

0.743625

0.173635

1.85037

0.024793

0.858662

0.520534

1

1

1.3

88444.11

5.82

0

0.47

1.52441

0.198332

1.30794

0.161745

1.10967

0.842203

0.75631

0.270835

137008.8

1

1

4.0

5.63

0

0.174

2.06532

0.007643

0.682674

0.092343

1.35808

0.376098

0.677579

0.145969

3

3

6.8

102593

5.25

0

0.806

1.32235

0.441078

0.897582

0.585148

1.36717

0.362715

0.727133

0.217995

6

5

7.4

109699.9

4.85

0

0.424

1.24042

0.574662

0.858329

0.451087

1.45208

0.252337

0.940469

0.782576

5

3

10.6

8.14

0

1.033

1.48439

0.236366

0.858329

0.451087

1.00961

0.930757

0.78254

0.325308

2

2

3.1

104699

7.61

0

0.468

1.43234

0.293154

1.19362

0.379663

0.782743

0.428486

0.785338

0.331513

4

4

3.3

158681.8

6.76

0

0.6

1.37845

0.360916

1.11573

0.600452

1.47999

0.221791

0.964539

0.866495

8

6

10.5

96903.47

5.88

0

0.188

1.46552

0.255977

0.863622

0.468088

1.28186

0.499933

0.819045

0.412195

53

15

61.7

23314.87

4.66

0

0.865

1.44572

0.277749

1.01654

0.942624

1.33944

0.404486

0.924497

0.728192

1

1

5.8

31231.35

9

4

0.126

1.37723

0.362548

1.04859

0.827467

1.7506

0.048945

1.16982

0.544767

6

4

4.1

6.2

0

0.183

1.61623

0.128321

1.35509

0.10653

1.27835

0.506104

1.15906

0.570866

3

3

4.8

5.78

1

0.304

1.41079

0.319153

0.849696

0.424121

1.51087

0.191195

0.964276

0.865567

1

1

1.2

4.87

0

0.556

1.39572

0.338204

0.758197

0.199316

1.61925

0.108199

1.00884

0.980453

10

8

15.7

61334.55

4.63

0

0.911

1.47951

0.241333

0.95507

0.809047

1.50888

0.193067

0.992153

0.964601

4

3

8.7

52874.1

4.56

0

0.349

1.1298

0.780456

0.81304

0.320577

1.38138

0.342394

0.703244

0.180598

5

3

8.4

32939.8

5.88

0

0.292

1.63225

0.118369

1.20076

0.362277

1.00633

0.922665

1.02315

0.939291

8

4

37.4

21891.75

8.22

0

1.053

1.40427

0.32731

1.21099

0.338247

1.1114

0.83846

1.02564

0.932144

2

2

8.8

41164.16

7.62

0

0.452

0.96704

0.859394

1.94754

1.62E05

1.19827

0.657203

1.15135

0.589911

2

2

2.9

98817.56

6.03

0

0.233

1.51965

0.202609

1.16641

0.450479

1.23867

0.578659

0.901252

0.651493

54785.99

36984.28

156651 90959.88 145320.3

No. of Pages 73

B2RYW3_RAT

3.2

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

PTMS_RAT

1

NSC 16186

RTN4R_RAT

1

22 April 2015

PPP5_RAT

Copine 5 protein OS = Rattus norvegicus GN = Cpne5 PE = 2 SV = 1 Serine/threonine-protein phosphatase 5 OS = Rattus norvegicus GN = Ppp5c PE = 2 SV = 1 Reticulon-4 receptor OS = Rattus norvegicus GN = Rtn4r PE = 1 SV = 2 Dynactin subunit 1 OS = Rattus norvegicus GN = Dctn1 PE = 2 SV = 1 Cytochrome b-c1 complex subunit Rieske, mitochondrial OS = Rattus norvegicus GN = Uqcrfs1 PE = 1 SV = 2 Rho-related GTP-binding protein RhoB OS = Rattus norvegicus GN = Rhob PE = 1 SV = 1 Calsyntenin-1 OS = Rattus norvegicus GN = Clstn1 PE = 2 SV = 1 Protein Pkp4 OS = Rattus norvegicus GN = Pkp4 PE = 2 SV = 1 Protein Epb41l3 OS = Rattus norvegicus GN = Epb41l3 PE = 2 SV = 1 Alpha-actinin-4 OS = Rattus norvegicus GN = Actn4 PE = 1 SV = 2 Parathymosin OS = Rattus norvegicus GN = Ptms PE = 1 SV = 2 Phospholipase C delta 1 long form OS = Rattus norvegicus GN = Plcd1 PE = 2 SV = 1 Isoform 2 of Complement component receptor 1-like protein OS = Rattus norvegicus GN = Cr1l Protein Epb4.1l2 OS = Rattus norvegicus GN = Epb4.1l2 PE = 4 SV = 1 Protein Pcdh1 (Fragment) OS = Rattus norvegicus GN = Pcdh1 PE = 4 SV = 1 Protein Pcdh1 (Fragment) OS = Rattus norvegicus GN = Pcdh1 PE = 4 SV = 1 Phosphofurin acidic cluster sorting protein 1 OS = Rattus norvegicus GN = Pacs1 PE = 2 SV = 1 SH3 and multiple ankyrin repeat domains protein 2 OS = Rattus norvegicus GN = Shank2 PE = 1 SV = 2 Protein Icam5 OS = Rattus norvegicus GN = Icam5 PE = 4 SV = 1 Synaptosomal-associated protein 25 OS = Rattus norvegicus GN = Snap25 PE = 1 SV = 1 Membrane-associated ring finger (C3HC4) 5 OS = Rattus norvegicus GN = March5 PE = 2 SV = 1 Leucine-rich PPR motif-containing protein, mitochondrial OS = Rattus norvegicus GN = Lrpprc PE = 1 SV = 1 Neuroligin-2 OS = Rattus norvegicus GN = Nlgn2 PE = 1 SV = 1 Uncharacterized protein (Fragment) OS = Rattus norvegicus PE = 3 SV = 1 Neurofilament light polypeptide OS = Rattus norvegicus GN = Nefl PE = 1 SV = 3 Protein Ctnna2 OS = Rattus norvegicus GN = Ctnna2 PE = 4 SV = 1 3-mercaptopyruvate sulfurtransferase OS = Rattus norvegicus GN = Mpst PE = 1 SV = 3 NADH dehydrogenase (Ubiquinone) 1 beta subcomplex, 9 OS = Rattus norvegicus GN = Ndufb9 PE = 2 SV = 1 Rgs14 protein OS = Rattus norvegicus GN = Rgs14 PE = 2 SV = 1 Protein Pdpr OS = Rattus norvegicus GN = Pdpr PE = 3 SV = 1

20

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

D3ZGN2_RAT

Q68HB5_RAT G3V964_RAT EMAL1_RAT B2GV74_RAT D4A9C3_RAT D4A6R4_RAT F2Z3Q8_RAT DC1I1_RAT ABD12_RAT EMC8_RAT

HS71L_RAT OAT_RAT D4A0T0_RAT D4A8H3_RAT G3V8B6_RAT D4A565_RAT

Q63714_RAT SL9A1_RAT OGT1_RAT

D3ZZR9_RAT QCR6_RAT D3ZEI4_RAT

D4A1G8_RAT GMFB_RAT

0.611 0.339

1.71847 1.31876

0.074779 0.446532

1.24785 0.696924

0.26037 0.107888

0.977932 1.19094

0.852974 0.671913

0.982637 0.519136

0.930656 0.030475

16258.51

10.07

0

0.503

1.26809

0.527486

0.98839

0.947912

1.12444

0.810425

0.782919

0.326144

93518.01

4.76

0

0.095

1.56581

0.163919

1.16162

0.463704

1.72293

0.058401

1.40065

0.15017

5.05

2

0.484

1.78298

0.051591

0.955873

0.812344

2.05789

0.004837

1.3245

0.244407

38012.05

7.99

0

0.097

1.42494

0.301923

1.0253

0.910922

1.4078

0.306583

0.797103

0.358433

1.7

89800.69

6.56

0

0.393

1.5807

0.152707

1.18458

0.402386

1.357

0.377715

0.899598

0.646165

2

4.8

66943.6

6.58

0

0.698

1.49025

0.230492

0.979604

0.910965

1.27217

0.517078

0.780432

0.320683

7

5

13.8

42285.42

9.6

0

0.902

1.27676

0.513125

1.02114

0.925953

1.27214

0.517132

1.15161

0.589262

1

1

9.8

30458.04

6.92

0

0.397

1.49318

0.227595

0.922097

0.677304

1.47776

0.224136

1.0175

0.955551

2

2

2.9

97183.09

4.68

0

0.097

1.3254

0.436463

1.14722

0.504658

1.47071

0.231642

1.16064

0.567002

1

1

1.9

70306.76

5.07

0

0.594

1.52205

0.200444

0.835252

0.381177

1.49977

0.201818

1.12621

0.65401

2

2

7.8

45295.28

8.9

0

0.309

1.28115

0.505937

0.784583

0.252679

1.26068

0.537822

0.665045

0.131023

2

2

14.5

23405.26

5.72

0

0.368

1.26067

0.539939

1.21648

0.325775

0.980325

0.858808

0.821563

0.418655

1.3 3.1

1

1

9.3

1

1

1.6

1

1

1.3

13

7

20.4

1

1

2

140006.2 149647.2

135771

9

2

4.5

70548.35

5.91

0

0.387

1.58576

0.149033

1.12748

0.563743

1.5452

0.16096

1.20426

0.465407

8

5

14.4

48332.06

6.53

0

0.113

1.54739

0.178628

1.15186

0.49124

0.996666

0.898848

0.769976

0.298383

14

5

32.4

20858.36

7.57

0

0.937

1.25573

0.548313

0.978999

0.908427

1.72866

0.056327

1.23233

0.405816

1

1

1.2

117929.5

5.73

0

0.246

1.9089

0.023326

1.24382

0.268215

2.434

0.000115

2.55437

2.10E-08

1

1

1.5

105698.9

5.25

0

0.227

1.21793

0.614432

1.22566

0.305623

1.19378

0.666208

1.12692

0.652163

14

6

27.0

9.46

0

0.252

1.51166

0.209929

1.07874

0.722373

1.44238

0.263614

1.20907

0.454864

1

1

0.4

5.01

0

0.912

1.40499

0.326398

1.09508

0.667397

1.16493

0.72507

0.882431

0.591945

2

1

1.6

6.71

13

0.209

1.52867

0.194568

1.10977

0.619444

0.810371

0.480222

0.609498

0.078582

1

1

0.9

115604.8

6.18

0

0.232

1.48709

0.233648

1.29712

0.177036

1.6902

0.071502

1.59761

0.031557

2

2

10.0

15387.8

9.05

0

0.172

1.33689

0.419369

1.00742

0.975718

1.35188

0.385409

0.914061

0.693363

21

3

37.1

10423.53

4.9

0

1.019

1.3891

0.346795

0.936334

0.73325

1.3861

0.335815

0.862006

0.530305

10

6

20.5

45999.26

9.66

0

0.524

1.28622

0.497686

0.906319

0.617327

1.46093

0.242352

0.852656

0.503217

11

3

8.5

36196.32

5.76

4

0.202

1.37206

0.369551

0.884257

0.537634

1.75041

0.049004

0.843147

0.476438

2

2

2.7

171693.2

6.29

0

0.88

1.19374

0.658493

0.668783

0.078973

1.15731

0.740909

0.97061

0.887943

1

1

7.0

16750

5.32

0

0.606

1.48598

0.234756

1.11965

0.588075

1.42042

0.29039

0.944836

0.797646

21663.84

364293.2 91645.93

21

(continued on next page)

No. of Pages 73

GPM6B_RAT

Heat shock 70 kDa protein 1-like OS = Rattus norvegicus GN = Hspa1l PE = 2 SV = 2 Ornithine aminotransferase, mitochondrial OS = Rattus norvegicus GN = Oat PE = 1 SV = 1 Protein Ndufb10 OS = Rattus norvegicus GN = Ndufb10 PE = 4 SV = 1 Protein Uba6 OS = Rattus norvegicus GN = Uba6 PE = 4 SV = 1 26S proteasome non-ATPase regulatory subunit 1 OS = Rattus norvegicus GN = Psmd1 PE = 4 SV = 1 NADH dehydrogenase (Ubiquinone) 1 beta subcomplex, 5 (Predicted), isoform CRA_b OS = Rattus norvegicus GN = Ndufb5 PE = 4 SV = 1 GCP360 OS = Rattus norvegicus GN = Golgb1 PE = 2 SV = 1 Sodium/hydrogen exchanger 1 OS = Rattus norvegicus GN = Slc9a1 PE = 1 SV = 2 UDP-N-acetylglucosamine–peptide Nacetylglucosaminyltransferase 110 kDa subunit OS = Rattus norvegicus GN = Ogt PE = 1 SV = 1 Peptidyl-prolyl cis-trans isomerase OS = Rattus norvegicus GN = Fkbp2 PE = 4 SV = 1 Cytochrome b-c1 complex subunit 6, mitochondrial OS = Rattus norvegicus GN = Uqcrh PE = 3 SV = 1 Protein Hepacam OS = Rattus norvegicus GN = Hepacam PE = 4 SV = 1 Neuronal membrane glycoprotein M6-b OS = Rattus norvegicus GN = Gpm6b PE = 4 SV = 1 Protein Cep170b OS = Rattus norvegicus GN = Cep170b PE = 2 SV = 1 Glia maturation factor beta OS = Rattus norvegicus GN = Gmfb PE = 2 SV = 1

0 0

1 2

NSC 16186

AP180_RAT

6.52 6.44

1 4

22 April 2015

RS14_RAT

Protein Cfh OS = Rattus norvegicus GN = Cfh PE = 2 SV = 1 Contactin-associated protein 1 (Fragment) OS = Rattus norvegicus GN = Cntnap1 PE = 2 SV = 1 40S ribosomal protein S14 OS = Rattus norvegicus GN = Rps14 PE = 2 SV = 3 Clathrin coat assembly protein AP180 OS = Rattus norvegicus GN = Snap91 PE = 1 SV = 1 Protein Pcdh7 OS = Rattus norvegicus GN = Pcdh7 PE = 2 SV = 1 Neurotrimin OS = Rattus norvegicus GN = Ntm PE = 4 SV = 1 Echinoderm microtubule-associated protein-like 1 OS = Rattus norvegicus GN = Eml1 PE = 2 SV = 2 Kinesin light chain 2 (Predicted), isoform CRA_b OS = Rattus norvegicus GN = Klc2 PE = 2 SV = 1 Protein Psd3 OS = Rattus norvegicus GN = Psd3 PE = 2 SV = 1 Protein LOC100362216 OS = Rattus norvegicus GN = LOC100362216 PE = 4 SV = 1 Importin subunit beta-1 OS = Rattus norvegicus GN = Kpnb1 PE = 4 SV = 1 Cytoplasmic dynein 1 intermediate chain 1 OS = Rattus norvegicus GN = Dync1i1 PE = 2 SV = 1 Monoacylglycerol lipase ABHD12 OS = Rattus norvegicus GN = Abhd12 PE = 2 SV = 1 ER membrane protein complex subunit 8 OS = Rattus norvegicus GN = Emc8 PE = 2 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

F1M983_RAT CNTP1_RAT

D3ZUJ5_RAT Q5VLR5_RAT G3V640_RAT G3V881_RAT MIC25_RAT

NDRG2_RAT D3ZP76_RAT

TSN2_RAT TBA1A_RAT B0K031_RAT SCRN1_RAT GABR2_RAT L1CAM_RAT VGLU1_RAT Q4KM69_RAT

D3Z8X2_RAT TBA3_RAT TBA1B_RAT KCC2A_RAT B1H2A6_RAT B5DF26_RAT D4A0T8_RAT

3HIDH_RAT MPP3_RAT CC50A_RAT

52008.43

7.81

0

0.172

1.72115

0.073671

1.16699

0.448919

1.4752

0.226841

1.02376

0.937552

12

5

14.5

37284.93

5.99

0

0.09

1.57282

0.158566

0.966132

0.854706

1.57355

0.138832

1.05022

0.861969

1

1

1.1

141398.2

5.9

0

0.276

1.38619

0.350621

1.19479

0.376778

1.28065

0.502049

1.03909

0.893657

1

1

4.7

23973.2

5.67

0

0.221

1.20668

0.634754

1.27749

0.207477

1.21642

0.62138

1.02148

0.944096

3 2

3 2

9.6 6.4

46877.51 51059.81

5.09 8.49

0 0

0.413 0.502

1.34598 1.30028

0.406126 0.475211

1.2689 1.05097

0.221927 0.819005

1.09675 1.07883

0.870193 0.909306

0.984492 0.839645

0.937267 0.466777

4

4

7.4

69830.97

8.63

0

0.04

1.46163

0.260163

1.11088

0.615882

1.33684

0.408559

0.896793

0.637165

5

4

19.8

20460.68

7.81

0

0.843

1.41804

0.310245

0.99898

0.992592

1.55483

0.153165

1.34998

0.209104

4

3

13.2

40778.74

5.16

0

0.272

1.34479

0.407849

1.08929

0.686686

1.85857

0.023374

1.2535

0.364033

1

1

3.3

52625.87

5.23

0

0.22

1.77416

0.054355

1.30733

0.162577

0.73822

0.352309

0.719554

0.205572

2

2

0.6

5.1

0

0.36

1.29897

0.477283

1.66163

0.002611

0.942172

0.7669

1.0088

0.980581

1

1

5.4

8.28

4

0.546

1.61637

0.128232

0.662015

0.073054

1.8491

0.025019

0.714966

0.198305

132

18

42.4

50135.07

4.94

0

0.229

1.37772

0.361891

1.15873

0.471767

1.41296

0.299902

1.21471

0.442675

3

2

11.2

30312.85

10.87

0

0.578

1.30208

0.472378

1.08492

0.701403

1.44161

0.264519

1.09218

0.744931

5

4

11.8

46395.51

4.73

0

0.428

1.32912

0.430883

1.07604

0.731601

1.61072

0.113467

1.04322

0.881871

1

1

1.9

105750.3

8.95

7

0.122

1.33981

0.415087

1.21532

0.328384

0.82505

0.509038

0.724114

0.212983

9

6

8.6

140876.7

5.51

0

0.477

1.43232

0.293176

1.04367

0.844966

1.21

0.633951

0.929441

0.744896

10

4

7.3

61664.67

6.96

10

0.225

1.3302

0.429282

1.04934

0.824789

1.6983

0.068052

1.23947

0.391403

1

1

5.7

37578.39

6.1

0

0.377

1.25758

0.545177

1.20907

0.342679

0.859976

0.581071

0.782235

0.324636

1

1

1.2

4.82

0

0.245

1.22156

0.607921

0.785508

0.254715

1.47741

0.224506

0.894777

0.630728

120

16

39.8

49958.99

4.98

0

0.185

1.3673

0.376078

1.11777

0.594007

1.30866

0.454083

1.06016

0.833861

135

19

42.6

50151.07

4.94

0

0.23

1.36858

0.374313

1.16373

0.457842

1.40612

0.308784

1.21569

0.440583

60

19

35.4

54114.1

6.61

0

0.386

1.44262

0.281269

1.26537

0.228077

1.62648

0.103885

1.36385

0.191529

1

1

2.7

74373.52

5.85

0

0.835

1.29038

0.490975

1.09891

0.654776

1.3004

0.467958

0.982164

0.928971

1

1

2.3

93861.36

7.08

0

0.679

1.67971

0.092404

1.41266

0.060629

1.09567

0.872539

0.98854

0.951702

1

1

2.7

38310.26

8.55

0

0.077

1.4388

0.285643

0.760966

0.204496

1.52472

0.178527

0.866247

0.542831

5

3

3.4

7.29

0

0.497

1.20712

0.633952

1.1073

0.627425

1.23215

0.591043

0.970291

0.886812

3

2

10.8

35302.37

8.73

0

0.031

1.47515

0.245831

1.14263

0.51809

1.38053

0.343588

1.26763

0.3377

5

4

8.0

66587.76

6.05

0

0.528

1.50818

0.213184

0.994263

0.972679

1.46789

0.234698

1.2296

0.411397

1

1

5.8

37172.11

8.98

2

0.353

0.687975

0.271538

0.930486

0.710076

1.65243

0.089513

0.824257

0.425635

459716.1 24189.26

108570.9

169858.9

No. of Pages 73

Q6TXE9_RAT

3.4

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

F1MAP9_RAT

1

NSC 16186

D3ZZB2_RAT

1

22 April 2015

OPCM_RAT

Uncharacterized protein (Fragment) OS = Rattus norvegicus PE = 4 SV = 1 Opioid-binding protein/cell adhesion molecule OS = Rattus norvegicus GN = Opcml PE = 4 SV = 1 Protein Pex1 OS = Rattus norvegicus GN = Pex1 PE = 3 SV = 1 Deoxythymidylate kinase (Predicted), isoform CRA_b OS = Rattus norvegicus GN = Dtymk PE = 3 SV = 1 BWK4 OS = Rattus norvegicus GN = Erp44 PE = 2 SV = 1 Mitochondrial import inner membrane translocase subunit TIM44 OS = Rattus norvegicus GN = Timm44 PE = 4 SV = 1 Leucine rich repeat neuronal 6A, isoform CRA_a OS = Rattus norvegicus GN = Lingo1 PE = 4 SV = 1 Coiled-coil-helix-coiled-coil-helix domain-containing protein 6, mitochondrial OS = Rattus norvegicus GN = Chchd6 PE = 2 SV = 1 Protein NDRG2 OS = Rattus norvegicus GN = Ndrg2 PE = 1 SV = 1 Protein Ttyh3 OS = Rattus norvegicus GN = Ttyh3 PE = 2 SV = 1 E3 ubiquitin-protein ligase HUWE1 OS = Rattus norvegicus GN = HUWE1 PE = 2 SV = 1 Tetraspanin-2 OS = Rattus norvegicus GN = Tspan2 PE = 1 SV = 1 Tubulin alpha-1A chain OS = Rattus norvegicus GN = Tuba1a PE = 1 SV = 1 60S ribosomal protein L7 OS = Rattus norvegicus GN = Rpl7 PE = 2 SV = 1 Secernin-1 OS = Rattus norvegicus GN = Scrn1 PE = 1 SV = 1 Gamma-aminobutyric acid type B receptor subunit 2 OS = Rattus norvegicus GN = Gabbr2 PE = 1 SV = 2 Neural cell adhesion molecule L1 OS = Rattus norvegicus GN = L1cam PE = 2 SV = 1 Vesicular glutamate transporter 1 OS = Rattus norvegicus GN = Slc17a7 PE = 1 SV = 1 COP9 (Constitutive photomorphogenic) homolog, subunit 5 (Arabidopsis thaliana) OS = Rattus norvegicus GN = Cops5 PE = 2 SV = 1 Protein Pcdh10 OS = Rattus norvegicus GN = Pcdh10 PE = 2 SV = 1 Tubulin alpha-3 chain OS = Rattus norvegicus GN = Tuba3a PE = 2 SV = 1 Tubulin alpha-1B chain OS = Rattus norvegicus GN = Tuba1b PE = 1 SV = 1 Calcium/calmodulin-dependent protein kinase type II subunit alpha OS = Rattus norvegicus GN = Camk2a PE = 1 SV = 1 Fxr2 protein OS = Rattus norvegicus GN = Fxr2 PE = 2 SV = 1 Similar to oxysterol-binding protein-like protein 8 isoform a OS = Rattus norvegicus GN = Osbpl8 PE = 2 SV = 1 Protein RGD1565002 OS = Rattus norvegicus GN = RGD1565002 PE = 3 SV = 1 Protein Eprs OS = Rattus norvegicus GN = Eprs PE = 2 SV = 1 3-hydroxyisobutyrate dehydrogenase, mitochondrial OS = Rattus norvegicus GN = Hibadh PE = 1 SV = 3 MAGUK p55 subfamily member 3 OS = Rattus norvegicus GN = Mpp3 PE = 1 SV = 3 Cell cycle control protein 50A OS = Rattus norvegicus GN = Tmem30a PE = 2 SV = 1

22

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

F1LN80_RAT

ACTB_RAT CSN8_RAT Q68G39_RAT NAC3_RAT F1LQL3_RAT G3V826_RAT ACTN1_RAT Q4V7D9_RAT F1LXD6_RAT Q3T1H3_RAT D3ZSY8_RAT D3ZN99_RAT GSK3B_RAT RALA_RAT STABP_RAT UBA1_RAT F1LQP0_RAT KAP0_RAT D3ZPJ0_RAT NUMBL_RAT UCHL3_RAT AT1A3_RAT D4A781_RAT CLCB_RAT

G3V963_RAT Q99NI1_RAT

0.625

0.932932

0.771908

1.05675

0.798622

0.974642

0.844965

0.723237

0.211543

9.45

0

0.928

1.39971

0.333086

0.926361

0.693889

1.22097

0.612542

0.824547

0.426388

11667.61

9.1

0

0.374

1.25562

0.548512

0.940031

0.748029

1.72749

0.056744

1.1419

0.613678

49.6

41736.29

5.29

0

0.2

1.39714

0.336377

1.06805

0.759153

1.3209

0.433968

0.986223

0.943437

1

6.2

23235.31

5.09

0

0.127

1.68906

0.087873

1.26676

0.225641

1.10531

0.85162

0.80568

0.3789

2

1

2.0

55874.28

7.23

0

0.446

1.40738

0.3234

1.17113

0.43769

1.44291

0.262979

1.1638

0.559294

1

1

1.3

103161.6

5.02

10

0.132

1.23012

0.592721

1.09287

0.674729

0.952954

0.792602

0.657733

0.122869

2

2

11.0

22318.9

10.81

0

0.605

1.36971

0.372767

1.03666

0.87003

1.4828

0.218877

1.08004

0.778298

9

5

10.7

71157.78

7.54

0

0.171

1.39909

0.33388

1.02698

0.904831

1.54434

0.16167

1.04212

0.885006

15

12

15.6

99808.87

5.41

0

0.577

1.3174

0.448602

0.865976

0.475762

1.26471

0.530505

0.913765

0.692385

1

1

2.2

51644.72

5.53

6

0.229

1.04295

0.954566

0.826364

0.356131

1.49856

0.203004

0.931172

0.750773

1

1

1.1

7.86

0

0.418

1.41981

0.308097

1.03811

0.864817

1.48294

0.218725

1.13525

0.630641

4.4

14

10

19.6

1

1

10.0

154

20

1

31619.69 100483.7

139593.1

33

13

18.9

93572.07

4.84

0

0.417

1.3472

0.404369

0.822788

0.346353

1.26959

0.521709

0.840389

0.46882

2

2

3.5

86648.14

9.19

0

0.584

1.50382

0.217301

0.931522

0.714165

1.33937

0.40461

1.00084

0.99563

1

1

1.2

7.49

0

0.188

1.30777

0.463467

1.04266

0.848576

1.46577

0.237004

0.814182

0.399884

1

1

5.7

46741.84

8.98

0

0.32

1.80051

0.04645

1.09058

0.682396

1.23168

0.591933

0.875138

0.569562

4

3

17.0

23552.5

6.66

0

0.621

1.44418

0.279497

1.01804

0.937163

1.56119

0.148173

1.0723

0.799814

1

1

2.8

48511.18

6.42

0

0.509

1.21128

0.62642

1.14545

0.509799

1.17796

0.698248

0.976047

0.90722

7

5

6.7

5.36

0

0.272

1.38033

0.358397

1.01477

0.949013

1.1578

0.739877

0.889423

0.613775

1

1

2.6

45489.28

5.66

0

0.637

1.17921

0.685554

0.9156

0.652328

1.43921

0.267369

0.860926

0.527138

6

3

9.7

43094.47

5.27

0

0.413

1.36687

0.376668

0.901784

0.600528

1.19441

0.66494

0.838227

0.462894

2

2

4.1

56422.2

9.91

0

0.399

1.37795

0.361586

1.03244

0.885165

1.05292

0.966203

0.724371

0.213407

2

2

4.7

65512.12

9.07

0

0.581

1.19368

0.658603

1.06348

0.775032

1.10838

0.844986

0.918858

0.709298

1

1

7.0

26123.32

5.01

0

0.393

1.48772

0.233012

1.32244

0.142855

0.824575

0.508092

0.81234

0.39528

200

44

41.5

111690.3

5.26

8

0.007

1.36492

0.379354

0.874667

0.504679

1.38741

0.333998

0.919092

0.710078

2

1

1.6

123704.8

4.85

0

0.133

1.82442

0.040137

1.39793

0.070439

0.728312

0.3366

1.07085

0.803882

1

1

4.4

25117.14

4.56

0

0.871

1.30967

0.460505

0.964161

0.84653

1.48906

0.212465

1.06031

0.833442

8

6

8.8

85719.37

6.94

0

0.132

1.4412

0.282895

1.08656

0.695862

1.11332

0.834321

0.752686

0.263832

2

2

2.8

5.3

0

0.25

1.30328

0.470478

1.2492

0.257778

1.14157

0.773968

0.886164

0.603556

1

1

8.3

5.98

0

0.021

1.06472

0.910369

0.921328

0.674327

1.49386

0.207646

1.17989

0.52089

169791.1

117786.4

110459.9 19088.75

23

(continued on next page)

No. of Pages 73

C7C5T2_RAT

0

1

NSC 16186

Q99PV2_RAT

5.88

1

22 April 2015

MAP6_RAT

Phosphatidylinositol transfer protein beta isoform OS = Rattus norvegicus GN = Pitpnb PE = 2 SV = 1 Microtubule-associated protein 6 OS = Rattus norvegicus GN = Map6 PE = 1 SV = 1 Protein Stxbp3 OS = Rattus norvegicus GN = Stxbp3 PE = 2 SV = 1 Actin, cytoplasmic 1 OS = Rattus norvegicus GN = Actb PE = 1 SV = 1 COP9 signalosome complex subunit 8 OS = Rattus norvegicus GN = Cops8 PE = 2 SV = 1 PCTAIRE protein kinase 1 OS = Rattus norvegicus GN = Cdk16 PE = 2 SV = 1 Sodium/calcium exchanger 3 OS = Rattus norvegicus GN = Slc8a3 PE = 2 SV = 1 60S ribosomal protein L18a (Fragment) OS = Rattus norvegicus GN = Rpl18a PE = 2 SV = 1 Transketolase OS = Rattus norvegicus GN = Tkt PE = 4 SV = 1 Alpha-actinin-1 (Fragment) OS = Rattus norvegicus GN = Actn1 PE = 2 SV = 1 Protein Smpdl3b OS = Rattus norvegicus GN = Smpdl3b PE = 2 SV = 1 Protein Pitpnm2 (Fragment) OS = Rattus norvegicus GN = Pitpnm2 PE = 2 SV = 1 Ncam1 protein OS = Rattus norvegicus GN = Ncam1 PE = 2 SV = 1 Protein Tbc1d10b OS = Rattus norvegicus GN = Tbc1d10b PE = 4 SV = 1 Protein Bai2 OS = Rattus norvegicus GN = Bai2 PE = 2 SV = 1 Glycogen synthase kinase-3 beta OS = Rattus norvegicus GN = Gsk3b PE = 1 SV = 1 Ras-related protein Ral-A OS = Rattus norvegicus GN = Rala PE = 1 SV = 1 STAM-binding protein OS = Rattus norvegicus GN = Stambp PE = 2 SV = 1 Ubiquitin-like modifier-activating enzyme 1 OS = Rattus norvegicus GN = Uba1 PE = 1 SV = 1 Cytohesin-3 (Fragment) OS = Rattus norvegicus GN = Cyth3 PE = 2 SV = 1 cAMP-dependent protein kinase type I-alpha regulatory subunit OS = Rattus norvegicus GN = Prkar1a PE = 2 SV = 2 Protein Shisa7 OS = Rattus norvegicus GN = Shisa7 PE = 2 SV = 1 Numb-like protein OS = Rattus norvegicus GN = Numbl PE = 1 SV = 1 Ubiquitin carboxyl-terminal hydrolase isozyme L3 OS = Rattus norvegicus GN = Uchl3 PE = 1 SV = 1 Sodium/potassium-transporting ATPase subunit alpha-3 OS = Rattus norvegicus GN = Atp1a3 PE = 1 SV = 2 Protein Ipo5 OS = Rattus norvegicus GN = Ipo5 PE = 4 SV = 1 Clathrin light chain B OS = Rattus norvegicus GN = Cltb PE = 1 SV = 1 6-phosphofructokinase OS = Rattus norvegicus GN = Pfkp PE = 2 SV = 1 RCG47487, isoform CRA_b OS = Rattus norvegicus GN = Tmem132a PE = 4 SV = 1 Nucleoside diphosphate kinase DR-nm23 OS = Rattus norvegicus GN = Nme3 PE = 2 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

PIPNB_RAT

AT1A2_RAT B5DF52_RAT D3ZWW3_RAT D3ZNZ8_RAT

CTNB1_RAT ECI2_RAT

F1LS79_RAT D3ZES7_RAT Q3SWU5_RAT VATL_RAT GBLP_RAT EAA1_RAT RS3A_RAT D3ZPC5_RAT IRGM_RAT CLVS1_RAT E9PSJ4_RAT B2RYT7_RAT SYNJ1_RAT BSN_RAT D3ZQP6_RAT D4A4M0_RAT

F1M6T7_RAT D4ADS4_RAT G3V6P8_RAT

89347.81

5.14

0

0.351

1.38893

0.347024

1.1382

0.531257

1.26256

0.534387

1.18382

0.511713

3

2

13.3

32909.37

5.43

0

0.641

1.25787

0.544683

0.954723

0.807624

0.871159

0.605105

0.760691

0.279469

9

4

8.8

48898.78

8.9

0

0.165

1.52716

0.195897

1.16407

0.456923

1.50133

0.200303

0.995028

0.974874

144

37

34.8

5.35

0

0.001

1.35427

0.394281

0.88386

0.536248

1.34342

0.398331

0.976457

0.908674

1

1

4.3

9.09

0

0.138

1.19994

0.647068

0.918129

0.662004

1.26409

0.531614

0.861921

0.530057

1

1

0.7

9.29

0

0.456

1.44312

0.280705

1.46912

0.032896

1.38759

0.333744

1.43412

0.118815

1

1

13.1

9.44

0

0.467

1.37352

0.367563

0.930407

0.709765

1.3287

0.421413

0.820767

0.416607

112129 35178.58 114478.5 9470.05

10

5

9.1

85453.59

5.53

0

0.178

1.26176

0.538104

0.995559

0.978148

0.809136

0.477839

0.657659

0.122788

4

3

8.7

43020.9

9.11

0

0.242

1.45818

0.263911

1.42322

0.054319

1.26138

0.536541

1.17301

0.537144

3

2

32.4

9.34

0

0.494

1.00707

0.964249

1.17739

0.421041

2.10203

0.003286

2.20621

1.38E05

2

2

1.3

252005

5.27

0

0.157

1.16315

0.71593

0.862628

0.464868

1.19501

0.663741

0.786167

0.333366

4

4

3.1

212608.9

6.44

0

0.23

1.26015

0.540822

1.0273

0.903678

1.04167

0.990993

0.857647

0.517585

5

3

8.7

40106.88

5.12

0

0.405

1.33846

0.41707

1.12039

0.585749

1.27568

0.510828

0.936601

0.769294

1

1

11.6

15807.75

9.1

4

1.075

1.52376

0.198917

1.16609

0.451368

1.0068

0.923816

1.06299

0.825882

1

1

5.1

35076.33

7.6

0

0.251

1.01246

0.978436

0.739516

0.16686

1.07779

0.911579

0.693602

0.166935

16

4

13.1

59696.84

8.51

6

0.379

1.29243

0.487686

0.796929

0.280796

1.43637

0.270766

0.810997

0.391942

2

1

5.3

29944.59

9.75

0

0.626

1.15472

0.732081

0.987015

0.942121

0.965467

0.822714

0.933127

0.757428

9

5

15.9

53802.3

6.58

0

0.137

1.4048

0.326634

0.771918

0.225936

1.19779

0.658168

0.780245

0.320276

1

1

3.9

46337.28

8.39

0

0.134

1.27875

0.509856

0.96148

0.835437

1.14573

0.765199

0.777885

0.315152

1

1

5.1

40665.99

6.32

0

0.368

1.4749

0.246088

0.93064

0.710683

1.99099

0.008464

1.47148

0.090142

1

1

1.5

77754.21

4.93

0

0.382

1.25537

0.54894

0.970418

0.87254

1.41248

0.300512

1.00623

0.987987

4

2

14.3

27793.54

6.5

0

0.082

1.18324

0.677998

1.17705

0.421933

0.862056

0.585508

0.753805

0.265981

8

6

5.7

144521.4

6.97

0

0.358

1.36762

0.375626

1.07963

0.719334

1.38717

0.33433

1.11512

0.683148

43

32

11.7

416591.8

7.37

0

0.828

1.32334

0.439571

0.877371

0.513863

1.4326

0.275323

0.980286

0.922287

2

2

5.9

75143.16

7.09

0

0.457

1.32042

0.444005

1.00206

0.995179

0.982231

0.863463

0.757317

0.272803

4

3

8.8

58181.89

9.51

0

0.447

1.38486

0.352378

1.06721

0.762076

1.03849

0.998002

0.762566

0.283222

2

1

2.4

66923.68

5.68

0

0.563

1.28521

0.499334

0.928836

0.703585

1.09222

0.880056

0.739825

0.239992

1

1

5.5

33328.31

4.62

0

1.016

1.22265

0.605986

0.873869

0.501985

1.21592

0.622369

0.708547

0.188457

21

2

15.8

16732.33

9.54

0

0.226

1.15972

0.72249

1.14889

0.499805

1.82417

0.029837

1.41488

0.136143

9

3

59.7

7985.1

9.14

0

0.465

1.45168

0.271069

1.13379

0.544499

1.06905

0.930738

0.845944

0.484232

8254.55

No. of Pages 73

CRTC1_RAT

19.7

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

ATP5I_RAT

Catenin beta-1 OS = Rattus norvegicus GN = Ctnnb1 PE = 1 SV = 1 Enoyl-CoA delta isomerase 2, mitochondrial OS = Rattus norvegicus GN = Eci2 PE = 1 SV = 1 ATP synthase subunit e, mitochondrial OS = Rattus norvegicus GN = Atp5i PE = 1 SV = 3 Chondroitin sulfate proteoglycan 4 OS = Rattus norvegicus GN = Cspg4 PE = 2 SV = 1 Uncharacterized protein OS = Rattus norvegicus GN = Plxna4a PE = 4 SV = 1 Protein kinase, cAMP dependent regulatory, type I, beta OS = Rattus norvegicus GN = Cyp4f18 PE = 2 SV = 1 V-type proton ATPase 16 kDa proteolipid subunit OS = Rattus norvegicus GN = Atp6v0c PE = 2 SV = 1 Guanine nucleotide-binding protein subunit beta-2-like 1 OS = Rattus norvegicus GN = Gnb2l1 PE = 1 SV = 3 Excitatory amino acid transporter 1 OS = Rattus norvegicus GN = Slc1a3 PE = 1 SV = 2 40S ribosomal protein S3a OS = Rattus norvegicus GN = Rps3a PE = 1 SV = 2 Protein Igsf8 OS = Rattus norvegicus GN = Igsf8 PE = 2 SV = 1 Immunity-related GTPase family M protein OS = Rattus norvegicus GN = Irgm PE = 2 SV = 1 Clavesin-1 OS = Rattus norvegicus GN = Clvs1 PE = 1 SV = 1 Protein Spag9 OS = Rattus norvegicus GN = Spag9 PE = 2 SV = 1 Haloacid dehalogenase-like hydrolase domain containing 3 OS = Rattus norvegicus GN = Hdhd3 PE = 2 SV = 1 Isoform 2 of Synaptojanin-1 OS = Rattus norvegicus GN = Synj1 Protein bassoon OS = Rattus norvegicus GN = Bsn PE = 2 SV = 1 Protein Sema7a OS = Rattus norvegicus GN = Sema7a PE = 4 SV = 1 Protein Shisa6 OS = Rattus norvegicus GN = Shisa6 PE = 4 SV = 1 CREB-regulated transcription coactivator 1 OS = Rattus norvegicus GN = Crtc1 PE = 1 SV = 1 Protein Erich5 OS = Rattus norvegicus GN = Erich5 PE = 4 SV = 1 Protein Mgst3 OS = Rattus norvegicus GN = Mgst3 PE = 4 SV = 1 Guanine nucleotide-binding protein subunit gamma OS = Rattus norvegicus GN = Gng12 PE = 3 SV = 1

10

NSC 16186

G3V6P2_RAT

15

22 April 2015

CAZA1_RAT

Transitional endoplasmic reticulum ATPase OS = Rattus norvegicus GN = Vcp PE = 1 SV = 3 F-actin-capping protein subunit alpha-1 OS = Rattus norvegicus GN = Capza1 PE = 1 SV = 1 Dihydrolipoamide S-succinyltransferase (E2 component of 2oxo-glutarate complex), isoform CRA_a OS = Rattus norvegicus GN = Dlst PE = 3 SV = 1 Sodium/potassium-transporting ATPase subunit alpha-2 OS = Rattus norvegicus GN = Atp1a2 PE = 2 SV = 1 C1q and tumor necrosis factor related protein 4 OS = Rattus norvegicus GN = C1qtnf4 PE = 2 SV = 1 Protein Rasal3 OS = Rattus norvegicus GN = Rasal3 PE = 4 SV = 1 40S ribosomal protein S27 OS = Rattus norvegicus GN = Rps27l2 PE = 3 SV = 1

24

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

TERA_RAT

RL8_RAT Q5PPH9_RAT

G3V758_RAT CADM3_RAT F1LT49_RAT ODBA_RAT

D3ZQ23_RAT G3V644_RAT

THIL_RAT ECH1_RAT D3Z8I7_RAT GNAI1_RAT ENOG_RAT GBG7_RAT

ODP2_RAT

B5DFJ4_RAT D4A921_RAT F1LTQ2_RAT D3ZT20_RAT THIKA_RAT ERMP1_RAT

SNIP1_RAT GUAD_RAT

0.635

1.3521

0.397357

1.04494

0.84044

1.15798

0.739512

0.900932

0.650462

113493.1

5.77

0

0.309

1.38108

0.3574

0.965631

0.852626

1.29835

0.471431

0.878576

0.580063

622450.4

5.28

0

0.635

1.57616

0.156064

1.25526

0.246336

1.33851

0.405941

0.759671

0.277443

28024.32

11.04

0

0.528

1.24904

0.559755

1.14256

0.518288

1.21875

0.616854

0.885525

0.601562

28565.24

3.98

0

1.206

1.4802

0.240629

0.761263

0.205056

1.47728

0.224644

0.937409

0.772065

7.57

0

0.324

1.15884

0.724174

0.924051

0.684883

1.20014

0.653475

0.944353

0.795975

42905.73

5.5

1

0.295

1.31589

0.450917

0.741743

0.170506

1.47881

0.223029

0.996397

0.979764

1.7

63629.47

8.52

0

0.416

1.42952

0.296473

1.07679

0.729046

1.11537

0.829899

0.755769

0.269781

1

3.6

50163.89

7.68

0

0.594

0.762919

0.394315

0.824495

0.350998

1.01717

0.949429

1.26106

0.349783

3

3

3.0

128317.2

5.68

0

0.983

1.14127

0.758064

0.848571

0.420678

1.29053

0.484831

0.73191

0.226098

6

4

8.5

49299.2

8.82

0

0.913

1.33121

0.427772

1.17021

0.440172

1.36573

0.364824

1.17097

0.542009

13

7

19.1

44694.51

8.92

0

0.086

1.44225

0.281691

1.17758

0.420557

1.00374

0.916275

1.31191

0.263327

1

1

3.4

36171.3

8.14

0

0.097

1.1732

0.696865

0.872363

0.496925

1.65697

0.087171

1.15791

0.573684

2

2

10.5

23380.84

9.3

0

0.267

1.23574

0.582844

1.15356

0.4864

1.33191

0.416325

1.107

0.704794

35

10

28.0

40344.64

5.69

0

0.32

1.47663

0.2443

1.03202

0.886695

1.42893

0.279804

1.1294

0.645717

19

11

27.2

47139.99

5.03

0

0.183

1.28286

0.503147

1.12846

0.560733

1.31345

0.446151

1.10787

0.70246

5

1

20.6

7523.65

8.71

0

0.335

1.25442

0.550547

0.856583

0.445557

1.35431

0.381742

1.00684

0.986231

23

12

18.8

67165.04

8.76

0

0.017

1.27995

0.507901

1.43714

0.046849

1.54527

0.160905

1.46697

0.093277

1

1

1.2

5.71

0

0.266

1.26426

0.533907

0.924767

0.687673

1.19819

0.657371

0.867421

0.546324

1

1

2.2

83429.61

7.85

0

0.281

0.956762

0.832797

0.816272

0.328979

1.02432

0.967141

0.704564

0.18253

38

3

11.0

34432.01

5.32

0

0.232

1.33028

0.42916

1.02142

0.924949

1.39992

0.317003

1.00919

0.979466

1

1

1.3

92692.03

8.74

0

0.343

1.37751

0.362183

0.911879

0.638199

1.19899

0.655782

0.864294

0.537044

1

1

5.6

38117.96

8.56

0

0.087

1.31268

0.45586

0.724212

0.143371

1.01949

0.955169

0.61581

0.083507

2

2

2.6

99895.6

6.82

8

0.184

1.282

0.504546

1.11084

0.616014

1.40337

0.312409

1.02128

0.944677

26

8

16.7

53592.45

7.39

0

0.42

1.55503

0.172409

1.51285

0.019673

1.50767

0.194218

1.7957

0.004169

22

12

13.9

9.33

0

0.685

1.22188

0.607357

1.00107

0.998781

1.38233

0.341067

0.857597

0.51744

6

5

12.3

5.56

0

0.192

1.27123

0.522264

1.11596

0.599727

1.49742

0.204118

0.997279

0.982917

13.5

24

15

19.8

1

1

0.3

1

1

6.2

1

1

4.9

2

2

3.9

11

8

29.0

1

1

1

11470.14

113046.5

110184.3

134837.1 51015.52

25

(continued on next page)

No. of Pages 73

F1LUE2_RAT

0

2

NSC 16186

D3ZD86_RAT

10.34

3

22 April 2015

CNTN1_RAT

Protein Mrps36 OS = Rattus norvegicus GN = Mrps36 PE = 2 SV = 1 Contactin-1 OS = Rattus norvegicus GN = Cntn1 PE = 1 SV = 2 Uncharacterized protein OS = Rattus norvegicus PE = 2 SV = 1 60S ribosomal protein L8 OS = Rattus norvegicus GN = Rpl8 PE = 2 SV = 2 Acidic (Leucine-rich) nuclear phosphoprotein 32 family, member A OS = Rattus norvegicus GN = Anp32a PE = 2 SV = 1 Contactin 2 OS = Rattus norvegicus GN = Cntn2 PE = 4 SV = 1 Cell adhesion molecule 3 OS = Rattus norvegicus GN = Cadm3 PE = 2 SV = 1 Protein Lrrc47 (Fragment) OS = Rattus norvegicus GN = Lrrc47 PE = 4 SV = 1 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial (Fragment) OS = Rattus norvegicus GN = Bckdha PE = 1 SV = 1 ELKS/Rab6-interacting/CAST family member 1 OS = Rattus norvegicus GN = Erc1 PE = 2 SV = 1 NADH dehydrogenase (Ubiquinone) flavoprotein 3-like, isoform CRA_a OS = Rattus norvegicus GN = Ndufv3 PE = 4 SV = 1 Acetyl-CoA acetyltransferase, mitochondrial OS = Rattus norvegicus GN = Acat1 PE = 1 SV = 1 Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial OS = Rattus norvegicus GN = Ech1 PE = 1 SV = 2 Glutathione S-transferase theta-1 OS = Rattus norvegicus GN = Gstt1 PE = 4 SV = 1 Guanine nucleotide-binding protein G(i) subunit alpha-1 OS = Rattus norvegicus GN = Gnai1 PE = 1 SV = 3 Gamma-enolase OS = Rattus norvegicus GN = Eno2 PE = 1 SV = 2 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 OS = Rattus norvegicus GN = Gng7 PE = 2 SV = 2 Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial OS = Rattus norvegicus GN = Dlat PE = 1 SV = 3 Protein Vps18 OS = Rattus norvegicus GN = Vps18 PE = 2 SV = 1 Protein Trim46 OS = Rattus norvegicus GN = Trim46 PE = 2 SV = 1 Uncharacterized protein (Fragment) OS = Rattus norvegicus PE = 3 SV = 1 Uncharacterized protein OS = Rattus norvegicus PE = 4 SV = 1 Isoform 2 of 3-ketoacyl-CoA thiolase A, peroxisomal OS = Rattus norvegicus GN = Acaa1a Endoplasmic reticulum metallopeptidase 1 OS = Rattus norvegicus GN = Ermp1 PE = 1 SV = 1 Calcium/calmodulin-dependent protein kinase type II subunit gamma (Fragment) OS = Rattus norvegicus GN = Camk2g PE = 2 SV = 1 Protein Snip OS = Rattus norvegicus GN = Snip PE = 2 SV = 1 Guanine deaminase OS = Rattus norvegicus GN = Gda PE = 1 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

D3ZZ41_RAT

KAD1_RAT DREB_RAT D3ZP47_RAT G3V8F1_RAT A1I3_RAT PPM1A_RAT D3ZCZ9_RAT MCCB_RAT

D3ZUR9_RAT PROF1_RAT D4A5X7_RAT

F1LWE3_RAT C2D1A_RAT TBA4A_RAT HINT3_RAT F1M745_RAT D3ZI16_RAT

D4A9F4_RAT AT1A1_RAT MAP2_RAT B5DF50_RAT ESTD_RAT Q9JMG8_RAT

EIF3I_RAT D3ZEG5_RAT

3

3

3.5

6

4

5.1

7

5

32.0

12 4

6 2

2

69946.25

6.66

10

0.43

1.42002

0.307841

0.978485

0.906269

1.20426

0.645291

0.87829

0.579185

109340.9

7.45

0

0.207

1.29411

0.485005

1.10485

0.635355

1.19306

0.66764

1.0078

0.983469

129701

6.62

0

0.018

1.33738

0.418654

1.05109

0.818581

1.33347

0.413854

0.728251

0.219872

21583.52

7.66

0

0.43

1.35191

0.397637

1.51853

0.018355

1.65882

0.08623

2.14985

3.42E05

11.4 16.9

72600.7 14010.4

4.4 5.27

0 0

0.796 0.683

1.26444 1.21693

0.533602 0.616227

0.81448 0.982566

0.324302 0.923403

1.11782 1.12208

0.824623 0.81548

0.744467 0.893384

0.248415 0.626299

2

4.1

71075.85

6.17

0

0.492

1.12846

0.783079

1.27793

0.206765

1.16029

0.734701

1.1475

0.599541

5

2

2.2

5.7

0

0.216

1.2853

0.499186

1.44416

0.043418

1.15607

0.743496

1.56611

0.041726

3

3

11.0

42416.22

5.19

0

0.493

1.21536

0.619051

1.04265

0.848608

1.04253

0.98908

0.798848

0.362539

14

6

59.5

13039.69

9.33

0

0.522

1.25594

0.547968

0.723497

0.14234

1.14965

0.756945

0.75493

0.268154

6

4

5.9

61516.44

8.56

0

0.178

1.34743

0.404039

1.05371

0.809346

1.09523

0.873509

0.852566

0.502959

6

4

5.8

98250.41

6.07

0

0.494

1.26637

0.530359

1.20141

0.360723

0.905064

0.680539

1.03133

0.915851

1

1

1.7

5.41

0

0.22

0.904282

0.700552

0.748243

0.181492

2.16811

0.001796

1.11004

0.69668

7 10

2 5

22.9 14.0

8.46 8.86

2 2

0.031 0.394

1.41228 1.28879

0.317311 0.493531

1.40037 0.978039

0.068728 0.904403

1.05838 1.76401

0.954198 0.044843

1.06076 1.38893

0.832178 0.162529

2

1

0.7

161459.5

7.57

0

0.753

1.18794

0.669246

1.00145

0.997382

1.23711

0.581611

0.920674

0.715365

1

1

1.8

103585.7

8.26

0

0.593

1.05076

0.938687

0.704957

0.117525

1.14769

0.761074

0.847722

0.489225

122

20

45.8

49923.86

4.95

0

0.252

1.26504

0.532601

1.19577

0.374368

1.24002

0.576111

1.09068

0.749018

2

2

23.4

19693.33

6.23

0

0.289

1.11063

0.818262

0.971881

0.878642

1.22375

0.607154

0.862725

0.532418

5

4

8.5

81633.23

5.92

0

0.649

1.20583

0.636305

0.859612

0.455175

1.57499

0.137778

1.31097

0.264771

1

1

2.3

37701.86

5.75

0

0.019

1.27733

0.512189

0.953976

0.804564

1.4899

0.211613

1.03545

0.90405

2

2

4.8

66163.26

5.81

0

0.452

1.119

0.801689

1.06075

0.784586

1.22868

0.597666

0.937557

0.772573

129

32

30.7

113053

5.3

10

0.002

1.27399

0.517688

0.83158

0.370702

1.47412

0.227994

0.979436

0.919264

33

22

17.9

199050.5

4.73

0

0.802

1.24731

0.562744

0.99435

0.973046

1.41171

0.30151

1.04667

0.872038

1

1

2.6

60415.95

8.35

0

0.564

1.17284

0.697549

1.35028

0.111375

0.911497

0.695249

1.08146

0.774396

3

3

13.5

31363.33

6.44

0

0.263

1.44307

0.280753

0.824163

0.350091

1.01733

0.949841

1.02105

0.945346

8

7

15.8

61394.45

6.5

0

0.162

1.40827

0.322285

0.995535

0.978049

1.23688

0.582049

0.951395

0.820419

16

13

4.3

6

0

0.806

1.27868

0.509971

0.958651

0.823764

1.29568

0.475986

0.832529

0.447481

1

1

3.4

36460.38

5.38

0

0.408

1.24417

0.56816

0.841237

0.398637

1.60902

0.114545

1.04416

0.879192

9

7

11.4

96201.63

6.18

0

0.643

1.20785

0.632626

0.80301

0.295399

1.35584

0.379451

1.04484

0.877252

163771.4

117272.2 14957.06 41216.11

530146.2

No. of Pages 73

PCLO_RAT

5.4

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

F1LRI7_RAT

3

NSC 16186

F1M585_RAT

4

22 April 2015

Q63116_RAT

Sodium- and chloride-dependent GABA transporter 3 OS = Rattus norvegicus GN = Slc6a11 PE = 2 SV = 1 Tyrosine-protein kinase receptor OS = Rattus norvegicus GN = Kit PE = 2 SV = 1 Protein Atp8a1 OS = Rattus norvegicus GN = Atp8a1 PE = 2 SV = 1 Adenylate kinase isoenzyme 1 OS = Rattus norvegicus GN = Ak1 PE = 1 SV = 3 Isoform E1 of Drebrin OS = Rattus norvegicus GN = Dbn1 Phosphohistidine phosphatase 1 (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Phpt1 PE = 4 SV = 1 Transporter OS = Rattus norvegicus GN = Slc6a7 PE = 3 SV = 1 Alpha-1-inhibitor 3 OS = Rattus norvegicus GN = A1i3 PE = 1 SV = 1 Protein phosphatase 1A OS = Rattus norvegicus GN = Ppm1a PE = 1 SV = 1 Protein LOC679739 OS = Rattus norvegicus GN = LOC679739 PE = 4 SV = 1 Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial OS = Rattus norvegicus GN = Mccc2 PE = 2 SV = 1 AP2-associated protein kinase 1 (Fragment) OS = Rattus norvegicus GN = Aak1 PE = 2 SV = 1 Leucyl-cystinyl aminopeptidase OS = Rattus norvegicus GN = Lnpep PE = 2 SV = 1 Profilin-1 OS = Rattus norvegicus GN = Pfn1 PE = 1 SV = 2 Ganglioside-induced differentiation-associated-protein 1 (Predicted) OS = Rattus norvegicus GN = Gdap1 PE = 4 SV = 1 Protein RGD1308124 (Fragment) OS = Rattus norvegicus GN = Nhsl1 PE = 2 SV = 1 Coiled-coil and C2 domain-containing protein 1A OS = Rattus norvegicus GN = Cc2d1a PE = 2 SV = 2 Tubulin alpha-4A chain OS = Rattus norvegicus GN = Tuba4a PE = 2 SV = 1 Histidine triad nucleotide-binding protein 3 OS = Rattus norvegicus GN = Hint3 PE = 2 SV = 2 Kinesin-like protein KIF2A (Fragment) OS = Rattus norvegicus GN = Kif2a PE = 2 SV = 1 COP9 (Constitutive photomorphogenic) homolog, subunit 6 (Arabidopsis thaliana) (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Cops6 PE = 4 SV = 1 Netrin G2 (Predicted), isoform CRA_b OS = Rattus norvegicus GN = Ntng2 PE = 4 SV = 1 Sodium/potassium-transporting ATPase subunit alpha-1 OS = Rattus norvegicus GN = Atp1a1 PE = 1 SV = 1 Isoform MAP2b of Microtubule-associated protein 2 OS = Rattus norvegicus GN = Map2 Protein Galnt2 (Fragment) OS = Rattus norvegicus GN = Galnt2 PE = 2 SV = 1 S-formylglutathione hydrolase OS = Rattus norvegicus GN = Esd PE = 1 SV = 1 Dihydropyrimidinase-related protein OS = Rattus norvegicus GN = Dpysl5 PE = 2 SV = 1 Isoform 2 of Protein piccolo OS = Rattus norvegicus GN = Pclo Eukaryotic translation initiation factor 3 subunit I OS = Rattus norvegicus GN = Eif3i PE = 2 SV = 1 Protein Gprin1 OS = Rattus norvegicus GN = Gprin1 PE = 4 SV = 1

26

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

S6A11_RAT

OLA1_RAT F1M9A2_RAT UK114_RAT F1M4V9_RAT

GEPH_RAT PALM_RAT B7X6I3_RAT Q6P7A7_RAT ABCB9_RAT CRYL1_RAT RL24_RAT

SHAN1_RAT NLRX1_RAT GNAI3_RAT ENOB_RAT MAP4_RAT NCAM1_RAT CSRP1_RAT Q5PQK5_RAT AP2M1_RAT ARPC5_RAT D3ZPN0_RAT SC6A9_RAT COF1_RAT NEUM_RAT

AQP4_RAT PCYOX_RAT COPB_RAT

3.9

65401.59

6.45

0

0.191

1.32056

0.443789

0.922574

0.67915

1.2467

0.563602

0.836249

0.457512

11

5

17.2

40261.17

8.2

0

0.338

1.2955

0.482785

0.795502

0.277441

1.31769

0.43919

1.37921

0.173349

2

2

4.1

78452.44

5.67

0

0.3

1.37547

0.364922

1.12891

0.559371

1.26659

0.527107

0.979359

0.918991

1

1

4.6

44534.78

7.62

0

0.387

1.26275

0.53645

1.34588

0.115943

1.4044

0.311055

1.3708

0.183131

19

8

13.4

5.1

0

0.109

1.23981

0.575738

0.993074

0.967662

1.0491

0.974622

0.78006

0.319872

2

1

7.3

14303.28

7.8

0

0.216

1.22914

0.594455

1.0944

0.669664

1.50899

0.192967

1.248

0.37461

2

2

5.8

51680.93

8.64

0

0.114

1.23378

0.586273

0.793306

0.272332

1.14778

0.760881

0.814843

0.401544

2 7

2 5

5.6 13.0

79747.52 37019.81

5.25 4.87

0 0

0.181 0.868

1.27031 1.34275

0.523791 0.41081

0.890234 0.728326

0.558706 0.149421

1.38781 1.03895

0.333439 0.996986

0.920393 0.740857

0.714423 0.241846

8

3

19.5

15042.83

9.01

1

0.6

1.33012

0.429393

1.22225

0.313007

1.31471

0.444069

1.04517

0.876313

6

5

11.2

68400.3

6.05

1

0.226

1.27027

0.523867

1.24815

0.259796

1.15199

0.75203

1.09325

0.741984

1

1

1.3

76376.42

6.18

0

0.281

1.63877

0.114492

1.04756

0.831123

1.20208

0.64963

0.839133

0.465373

100334.7

1

1

3.5

35340.66

5.94

0

0.103

0.965705

0.855932

2.34697

8.70E10

1.41039

0.303222

1.1444

0.60736

2

1

8.9

17778.75

11.26

0

0.926

1.24549

0.565884

0.986232

0.938825

1.0514

0.969556

0.869019

0.551097

SH3 and multiple ankyrin repeat domains protein 1 OS = Rattus norvegicus GN = Shank1 PE = 1 SV = 1 NLR family member X1 OS = Rattus norvegicus GN = Nlrx1 PE = 2 SV = 1 Guanine nucleotide-binding protein G(k) subunit alpha OS = Rattus norvegicus GN = Gnai3 PE = 1 SV = 3 Beta-enolase OS = Rattus norvegicus GN = Eno3 PE = 1 SV = 3 Microtubule-associated protein OS = Rattus norvegicus GN = Map4 PE = 2 SV = 1 Neural cell adhesion molecule 1 OS = Rattus norvegicus GN = Ncam1 PE = 1 SV = 1 Cysteine and glycine-rich protein 1 OS = Rattus norvegicus GN = Csrp1 PE = 2 SV = 2 Radixin OS = Rattus norvegicus GN = Rdx PE = 2 SV = 1 AP-2 complex subunit mu OS = Rattus norvegicus GN = Ap2m1 PE = 2 SV = 1 Actin-related protein 2/3 complex subunit 5 OS = Rattus norvegicus GN = Arpc5 PE = 1 SV = 3 Protein Pcdh17 OS = Rattus norvegicus GN = Pcdh17 PE = 4 SV = 1 Sodium- and chloride-dependent glycine transporter 1 OS = Rattus norvegicus GN = Slc6a9 PE = 2 SV = 1 Cofilin-1 OS = Rattus norvegicus GN = Cfl1 PE = 1 SV = 3 Neuromodulin OS = Rattus norvegicus GN = Gap43 PE = 1 SV = 1 Protein Emc1 OS = Rattus norvegicus GN = Emc1 PE = 2 SV = 1 Aquaporin-4 OS = Rattus norvegicus GN = Aqp4 PE = 2 SV = 1 Prenylcysteine oxidase OS = Rattus norvegicus GN = Pcyox1 PE = 1 SV = 1 Coatomer subunit beta OS = Rattus norvegicus GN = Copb1 PE = 1 SV = 1

9

6

4.3

226332.4

8.52

0

0.564

1.18468

0.675324

0.991948

0.962914

1.28833

0.488631

1.01242

0.97015

3

2

3.4

107588.6

7.36

0

0.096

1.21364

0.622154

0.999351

0.994157

1.41324

0.299532

0.969951

0.885609

24

4

11.6

40521.71

5.5

0

0.36

1.43354

0.291755

0.992608

0.965697

1.49393

0.207573

1.17972

0.521289

14 6

5 4

15.7 6.9

47013.35 95057.9

7.08 8.81

0 0

0.196 0.657

1.22381 1.45755

0.603922 0.264596

1.06872 1.24977

0.756812 0.256674

1.17744 1.18779

0.699308 0.678262

1.03916 1.07165

0.893452 0.801636

33

13

18.9

94657.19

4.83

0

0.433

1.2353

0.583611

0.856514

0.445337

1.17224

0.709983

0.896769

0.637088

4

2

14.0

20613.3

8.9

0

0.526

1.27226

0.520562

0.638455

0.055216

1.18734

0.679184

0.637209

0.102089

2 9

2 4

4.5 9.0

68542.98 49388.84

5.95 9.57

0 0

0.997 0.258

0.988887 1.27782

0.916429 0.511384

1.06564 0.846889

0.767513 0.41556

1.4745 1.1752

0.227582 0.703912

1.086 0.959597

0.761866 0.849109

2

2

21.2

16320.23

5.47

0

0.404

1.35735

0.389933

1.43661

0.047114

1.36199

0.370304

1.43573

0.117448

1

1

1.0

5.03

0

0.473

1.02063

1

0.839051

0.392205

1.30712

0.456649

0.802749

0.371827

2

1

3.5

70576.63

8.34

0

0.435

0.795642

0.457083

0.702295

0.114259

1.2216

0.611318

0.479758

0.019268

15 14

5 7

28.9 30.5

18532.31 23603.06

8.22 4.61

0 0

0.374 1.306

1.358 1.32676

0.389014 0.434422

1.09914 0.742172

0.654019 0.171217

1.48832 1.22253

0.213215 0.609513

1.38052 0.785072

0.171851 0.330918

1

1

1.7

6.86

0

0.066

1.42217

0.305241

1.02691

0.905105

0.972213

0.839061

0.771327

0.301204

2 1

2 1

6.6 3.6

5.75 6.61

0 0

0.461 0.099

1.1812 1.03466

0.681823 0.971424

1.01965 1.16177

0.931351 0.463286

1.62016 1.03824

0.107646 0.998541

1.14614 0.802139

0.602971 0.370365

1

1

1.4

5.66

0

0.093

1.51142

0.210155

1.45343

0.039222

0.737127

0.350554

0.890025

0.615674

130217.4

111495.8 35527.9 56286.98 107009.8

27

(continued on next page)

No. of Pages 73

D3ZFJ7_RAT

2

NSC 16186

D3ZWX4_RAT

2

22 April 2015

HPLN1_RAT

Glutamate decarboxylase 2 OS = Rattus norvegicus GN = Gad2 PE = 1 SV = 1 Hyaluronan and proteoglycan link protein 1 OS = Rattus norvegicus GN = Hapln1 PE = 1 SV = 2 Protein Nckipsd OS = Rattus norvegicus GN = Nckipsd PE = 4 SV = 1 Obg-like ATPase 1 OS = Rattus norvegicus GN = Ola1 PE = 2 SV = 1 Sodium/calcium exchanger 2 OS = Rattus norvegicus GN = Slc8a2 PE = 2 SV = 1 Ribonuclease UK114 OS = Rattus norvegicus GN = Hrsp12 PE = 1 SV = 3 Gamma-aminobutyric acid receptor subunit gamma-2 (Fragment) OS = Rattus norvegicus GN = Gabrg2 PE = 2 SV = 1 Isoform 5 of Gephyrin OS = Rattus norvegicus GN = Gphn Paralemmin, isoform CRA_b OS = Rattus norvegicus GN = Palm PE = 4 SV = 1 C38 protein OS = Rattus norvegicus GN = Cend1 PE = 2 SV = 1 Ribophorin I OS = Rattus norvegicus GN = Rpn1 PE = 2 SV = 1 Isoform 3 of ATP-binding cassette sub-family B member 9 OS = Rattus norvegicus GN = Abcb9 Lambda-crystallin homolog OS = Rattus norvegicus GN = Cryl1 PE = 2 SV = 3 60S ribosomal protein L24 OS = Rattus norvegicus GN = Rpl24 PE = 1 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

DCE2_RAT

F1LQN3_RAT F162A_RAT F1M3W5_RAT CHID1_RAT D4AD90_RAT ATCAY_RAT D3ZPF2_RAT F1LPB9_RAT GRP78_RAT

VPP1_RAT LRC73_RAT STIP1_RAT I6LBW6_RAT M0RC65_RAT E9PT79_RAT CXG2_RAT ISCA1_RAT D3Z941_RAT NDUS2_RAT

PECR_RAT G3V746_RAT F1LPS8_RAT B2RYU2_RAT QCR8_RAT NTRK3_RAT

COX41_RAT F1LTP6_RAT F1LM05_RAT

20598.99

9.15

2

0.119

1.8394

0.036565

1.20802

0.345103

1.33804

0.40668

1.17152

0.540691

4

3

9.3

45812.78

8.22

1

0.415

1.07087

0.897936

1.13059

0.554218

1.40742

0.307079

1.10421

0.712307

4

3

15.5

32800.98

6.88

0

0.461

1.08326

0.872959

1.12489

0.571749

1.23343

0.588592

1.1153

0.682679

8 1

6 1

6.9 7.7

126400.6 17826.76

4.41 10.02

0 1

0.407 0.512

1.25768 1.29279

0.545 0.487111

1.01652 1.17104

0.942678 0.437933

1.22067 1.66984

0.61312 0.080803

0.927126 1.63979

0.737058 0.021322

6

5

2.5

338164.9

5.94

0

0.309

1.16807

0.706571

1.04275

0.848221

1.14134

0.77445

0.904163

0.660919

3

2

4.3

44874.03

7.78

0

0.202

1.28482

0.499961

1.22824

0.300107

1.08366

0.898732

1.19295

0.490746

1

1

4.0

48974.45

9.06

0

0.216

1.76943

0.055886

0.861835

0.462309

1.35762

0.376795

0.993756

0.970328

1 1 8

1 1 6

2.7 4.2 17.0

42116.74 41831.79 75802.54

4.53 8.39 8.46

2 0 0

0.472 0.104 0.865

1.15472 1.21415 1.34824

0.732077 0.62123 0.402878

0.934439 0.941746 0.691896

0.725712 0.754916 0.102182

1.12336 1.01243 1.18668

0.812735 0.937711 0.680519

0.900184 0.665534 0.851997

0.648051 0.131583 0.501336

30

10

21.9

72346.1

5.07

0

0.481

1.24108

0.573521

1.21063

0.339078

1.02256

0.962783

0.987867

0.949302

1

1

0.6

178765.8

8.44

0

0.475

0.924194

0.749908

1.08345

0.706366

1.80266

0.034613

1.1901

0.497238

38

12

15.6

6.04

6

0.025

1.233

0.587655

1.06928

0.754899

0.913633

0.70016

0.749286

0.257377

96326.63

1

1

2.9

33376.7

4.83

0

0.005

1.13771

0.764995

0.858104

0.45037

1.57177

0.140149

0.993759

0.970338

4

3

5.2

62569.41

6.4

0

0.945

1.55919

0.169093

1.2081

0.344935

1.51197

0.190166

1.74467

0.007343

1

1

1.5

4.78

0

0.263

1.06304

0.913779

0.986048

0.938049

0.950746

0.787319

0.826969

0.432728

14

3

17.6

18578.17

7.88

0

0.402

1.21446

0.620673

1.09131

0.679934

1.43631

0.270841

1.24495

0.380575

1 2

1 1

5.4 3.4

31472.87 46989.76

9.35 6.72

0 3

0.207 0.212

1.23547 1.23564

0.583311 0.583024

1.55729 1.4676

0.011248 0.033468

0.585673 0.786645

0.160292 0.43559

0.785098 0.824301

0.330977 0.425748

1

1

11.6

14149.13

9.19

0

0.329

1.46982

0.251412

1.21739

0.323754

0.871306

0.605424

0.843285

0.476821

1 11

1 4

2.4 10.8

101580.4 52560.95

6.07 6.52

0 0

0.245 0.27

1.49457 1.24271

0.226234 0.570683

1.26484 1.00782

0.229011 0.97425

1.47083 1.02762

0.231518 0.975306

1.16278 0.821563

0.561763 0.418656

1

1

4.6

32432.78

8.89

0

0.007

1.04188

0.956745

1.23221

0.291739

0.846067

0.55182

0.76896

0.296273

5

4

3.6

6.41

0

0.388

1.2059

0.636179

1.19796

0.369034

0.892191

0.651467

1.02732

0.927342

3

2

11.8

34883.31

6.07

0

0.777

1.12355

0.792718

0.958312

0.822371

1.43924

0.267329

1.03689

0.899922

1

1

11.5

17845.41

9.48

0

0.363

1.32141

0.442497

1.4534

0.039233

1.45222

0.252181

1.1873

0.503669

14

2

25.6

9849.22

10.52

1

0.656

1.14595

0.748991

1.27881

0.205316

1.04636

0.980643

0.977584

0.912679

1

1

1.8

62758.6

5.81

0

0.138

1.12979

0.780457

0.669979

0.080058

1.09043

0.883949

0.682347

0.151986

1 3

1 3

4.2 7.0

37996.79 67848.31

5.24 5.22

0 0

0.119 0.328

1.1223 1.36007

0.795182 0.386116

1.7392 0.957204

0.00077 0.81781

0.687218 1.17035

0.276336 0.713874

0.460021 0.976376

0.015151 0.908387

52

10

38.5

19514.33

9.45

1

0.37

1.15658

0.7285

0.961919

0.837252

1.32

0.435428

0.939632

0.779696

7 1

4 1

16.5 1.6

38504.7 68165.54

7.11 5.31

0 0

0.113 0.196

1.20478 1.07665

0.638219 0.886262

1.17349 1.26522

0.431378 0.228334

1.15553 1.35347

0.744634 0.383004

1.13907 1.34045

0.620877 0.221854

101588.8

166027

No. of Pages 73

D4AC36_RAT D4A5J1_RAT

10.6

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Q2IBD4_RAT

2

NSC 16186

MFF_RAT

2

22 April 2015

CCD51_RAT

Signal peptidase complex catalytic subunit SEC11A OS = Rattus norvegicus GN = Sec11a PE = 2 SV = 1 Coiled-coil domain-containing protein 51 OS = Rattus norvegicus GN = Ccdc51 PE = 2 SV = 2 Mitochondrial fission factor OS = Rattus norvegicus GN = Mff PE = 4 SV = 1 Reticulon-4 OS = Rattus norvegicus GN = Rtn4 PE = 2 SV = 1 Protein FAM162A OS = Rattus norvegicus GN = Fam162a PE = 2 SV = 1 Protein Dmxl2 OS = Rattus norvegicus GN = Dmxl2 PE = 4 SV = 1 Chitinase domain-containing protein 1 OS = Rattus norvegicus GN = Chid1 PE = 2 SV = 2 Protein Agfg2 OS = Rattus norvegicus GN = Agfg2 PE = 4 SV = 1 Caytaxin OS = Rattus norvegicus GN = Atcay PE = 1 SV = 1 Protein Mcat OS = Rattus norvegicus GN = Mcat PE = 4 SV = 1 Rabphilin-3A OS = Rattus norvegicus GN = Rph3a PE = 2 SV = 1 78 kDa glucose-regulated protein OS = Rattus norvegicus GN = Hspa5 PE = 1 SV = 1 Cortactin binding protein 2 OS = Rattus norvegicus GN = Cttnbp2 PE = 4 SV = 1 V-type proton ATPase 116 kDa subunit a isoform 1 OS = Rattus norvegicus GN = Atp6v0a1 PE = 2 SV = 1 LLeucine-rich repeat-containing protein 73 OS = Rattus norvegicus GN = Lrrc73 PE = 2 SV = 1 Stress-induced-phosphoprotein 1 OS = Rattus norvegicus GN = Stip1 PE = 1 SV = 1 I6LBW6_RAT Protocadherin gamma a1 OS = Rattus norvegicus GN = Pcdhga1 PE = 2 SV = 1 Protein Cfl2 (Fragment) OS = Rattus norvegicus GN = Cfl2 PE = 4 SV = 1 Protein Tsn OS = Rattus norvegicus GN = Tsn PE = 2 SV = 1 Gap junction gamma-2 protein OS = Rattus norvegicus GN = Gjc2 PE = 1 SV = 2 Iron-sulfur cluster assembly 1 homolog, mitochondrial OS = Rattus norvegicus GN = Isca1 PE = 2 SV = 1 Protein Mars OS = Rattus norvegicus GN = Mars PE = 3 SV = 1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial OS = Rattus norvegicus GN = Ndufs2 PE = 1 SV = 1 Peroxisomal trans-2-enoyl-CoA reductase OS = Rattus norvegicus GN = Pecr PE = 2 SV = 1 Glutamate receptor ionotropic, NMDA 2B OS = Rattus norvegicus GN = Grin2b PE = 4 SV = 1 Transcriptional activator protein Pur-alpha OS = Rattus norvegicus GN = Pura PE = 2 SV = 1 RCG45615, isoform CRA_a OS = Rattus norvegicus GN = LOC685320 PE = 2 SV = 1 Cytochrome b-c1 complex subunit 8 OS = Rattus norvegicus GN = Uqcrq PE = 3 SV = 1 Isoform IC108 of NT-3 growth factor receptor OS = Rattus norvegicus GN = Ntrk3 Protein Eif3f OS = Rattus norvegicus GN = Eif3f PE = 4 SV = 1 Protein Kbtbd11 OS = Rattus norvegicus GN = Kbtbd11 PE = 4 SV = 1 Cytochrome c oxidase subunit 4 isoform 1, mitochondrial OS = Rattus norvegicus GN = Cox4i1 PE = 1 SV = 1 Enolase (Fragment) OS = Rattus norvegicus PE = 3 SV = 1 Protein LOC299282 OS = Rattus norvegicus GN = LOC299282 PE = 2 SV = 1

28

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

SC11A_RAT

MAP1A_RAT ALBU_RAT PDP1_RAT

GSH0_RAT D3ZTB4_RAT B2RZ13_RAT F1LPF3_RAT NHRF2_RAT Q6Q7Y5_RAT AINX_RAT KPCG_RAT D4ACG2_RAT NDUAB_RAT F1M951_RAT D3ZZ99_RAT D3Z981_RAT BEGIN_RAT D4A4D8_RAT B0BNE6_RAT

B4F7C7_RAT TAU_RAT F1LST4_RAT CSKI1_RAT GBB1_RAT

F1LPG5_RAT PPIF_RAT Q5M7T6_RAT

4.6

69286.83

5.83

0

0.972

1.15189

0.737527

0.976393

0.897503

1.38784

0.333407

0.939699

0.779925

2

2

5.0

68950.46

9.09

0

0.101

1.25262

0.553623

1.13954

0.527246

1.0701

0.928435

1.08404

0.767273

1

1

7.7

21388.63

7.02

0

0.37

1.10858

0.822333

0.534655

0.013645

1.33549

0.410678

0.661645

0.127181

38

20

9.9

4.89

0

0.833

1.16478

0.712841

0.884457

0.538332

1.10304

0.856541

0.895507

0.633056

47 3

19 2

32.2 5.4

68730.1 64744.67

6.09 6.44

0 0

0.38 0.407

1.18453 1.26358

0.675586 0.53504

1.73391 1.21621

0.00084 0.32638

1.32753 0.89187

0.423292 0.650747

1.81831 0.815585

0.003212 0.403413

1

1

5.8

30547.51

5.36

0

0.283

1.11393

0.81172

1.24587

0.264206

0.877952

0.619918

0.945712

0.800678

1

1

1.3

6.54

0

0.471

1.1228

0.794206

0.926869

0.695874

1.25443

0.549277

0.987895

0.949402

9

4

12.1

49474.71

9.31

7

0.356

1.19759

0.651389

0.925034

0.688711

1.09309

0.878162

0.8411

0.470776

3

3

6.7

71724.5

8.89

0

0.552

1.14303

0.754639

1.26523

0.228328

1.11709

0.826207

1.05471

0.84925

1

1

6.3

35217.08

8.28

0

0.823

0.947035

0.807801

1.02282

0.919863

1.66122

0.085025

1.47299

0.089114

22 20

3 10

8.2 26.7

44011.09 56114.7

8.41 5.2

0 0

0.395 0.649

1.31634 1.32214

0.45022 0.441396

0.974082 1.1201

0.887837 0.586656

1.52278 1.21218

0.180267 0.62967

1.16873 1.03215

0.547383 0.913483

324060.5

101170

20

13

25.4

78356.8

7.27

0

0.349

1.17922

0.685533

0.964255

0.84692

1.34839

0.390707

1.055

0.848422

2

2

4.0

72269.13

8.61

0

0.204

1.13742

0.765547

1.06618

0.765637

0.93516

0.750317

0.812327

0.395246

6

4

29.1

14853.9

8.3

2

0.157

1.15291

0.735563

1.35012

0.111538

1.14606

0.764496

1.15026

0.592628

2

2

1.7

182185.1

6.36

0

0.45

0.706303

0.298829

1.14407

0.513848

1.13162

0.795088

1.02032

0.947422

10

9

16.9

6.2

0

0.544

1.28807

0.494691

0.924282

0.685782

1.48896

0.212565

1.10506

0.710017

3

3

2.1

6.89

0

0.236

1.14157

0.75748

1.0751

0.734822

1.00732

0.925103

0.926305

0.734285

1

1

1.2

66161.36

5.49

0

0.744

1.16353

0.715222

0.906046

0.616309

1.28966

0.486339

0.933382

0.758297

3

3

8.0

42040.54

5

0

0.723

1.12383

0.792169

0.998892

0.992221

1.09799

0.867499

1.02028

0.947537

6

4

14.6

23970.05

5.87

0

0.374

1.11959

0.800522

0.946657

0.774742

1.39392

0.325084

1.23134

0.407831

1

1

6.3

21123.7

5.33

0

0.464

1.08475

0.869969

0.798698

0.284992

1.0912

0.882279

1.09625

0.73384

10

8

24.3

39151.41

9.51

0

0.832

1.14131

0.75798

1.0868

0.695053

1.51776

0.18482

1.20355

0.466981

10

8

11.4

78554.06

5.91

0

0.837

1.16648

0.709596

1.0868

0.695053

1.23033

0.594524

1.03858

0.895094

4 48

2 9

2.5 29.1

150345.4 37376.59

9.25 5.6

0 0

0.551 0.231

1.13932 1.11755

0.761866 0.804562

1.0313 0.994479

0.88928 0.97359

1.57784 1.09575

0.135698 0.872373

0.865117 0.962825

0.539479 0.860458

3

3

4.1

83360.59

9.06

5

0.366

1.22149

0.608061

1.07739

0.727

1.36411

0.367191

1.23554

0.399304

8

4

36.4

15064.16

9.82

0

0.676

1.08287

0.873732

1.00073

1

1.27716

0.508204

0.973684

0.898834

3

2

15.5

21809.74

9.3

0

0.164

1.16646

0.709633

1.15838

0.472732

1.07233

0.92354

0.88898

0.612384

14

9

20.5

40300.61

4.89

0

0.093

1.16897

0.704874

1.11566

0.600657

1.14353

0.769824

1.04975

0.863296

73150.98 210890.5

29

(continued on next page)

No. of Pages 73

LPPR4_RAT

3

NSC 16186

F1M8Y2_RAT

3

22 April 2015

ACADV_RAT

Ezrin (Fragment) OS = Rattus norvegicus GN = Ezr PE = 2 SV = 1 Very long-chain-specific acyl-CoA dehydrogenase, mitochondrial OS = Rattus norvegicus GN = Acadvl PE = 2 SV = 1 Protein Tspan7 (Fragment) OS = Rattus norvegicus GN = Tspan7 PE = 2 SV = 1 Microtubule-associated protein 1A OS = Rattus norvegicus GN = Map1a PE = 2 SV = 1 Serum albumin OS = Rattus norvegicus GN = Alb PE = 1 SV = 2 [Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 1, mitochondrial (Fragment) OS = Rattus norvegicus GN = Pdp1 PE = 3 SV = 1 Glutamate–cysteine ligase regulatory subunit OS = Rattus norvegicus GN = Gclm PE = 1 SV = 1 Protein Vps11 OS = Rattus norvegicus GN = Vps11 PE = 4 SV = 1 Gprc5b protein (Fragment) OS = Rattus norvegicus GN = Gprc5b PE = 2 SV = 1 Choline transporter-like protein 1 (Fragment) OS = Rattus norvegicus GN = Slc44a1 PE = 2 SV = 1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 OS = Rattus norvegicus GN = Slc9a3r2 PE = 2 SV = 1 Galpha13 OS = Rattus norvegicus GN = Gna13 PE = 2 SV = 1 Alpha-internexin OS = Rattus norvegicus GN = Ina PE = 1 SV = 2 Protein kinase C gamma type OS = Rattus norvegicus GN = Prkcg PE = 1 SV = 1 IlvB (Bacterial acetolactate synthase)-like (Predicted), isoform CRA_c OS = Rattus norvegicus GN = Ilvbl PE = 3 SV = 1 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 OS = Rattus norvegicus GN = Ndufa11 PE = 2 SV = 1 Tyrosine-protein phosphatase non-receptor type 23 OS = Rattus norvegicus GN = Ptpn23 PE = 2 SV = 1 Alpha-adducin OS = Rattus norvegicus GN = Add1 PE = 2 SV = 1 Uncharacterized protein OS = Rattus norvegicus GN = RGD1560871 PE = 4 SV = 1 Isoform 2 of Brain-enriched guanylate kinase-associated protein OS = Rattus norvegicus GN = Begain Uncharacterized protein OS = Rattus norvegicus GN = Palm2 PE = 4 SV = 1 NADH dehydrogenase (Ubiquinone) Fe-S protein 8 (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Ndufs8 PE = 2 SV = 1 Hebp1 protein OS = Rattus norvegicus GN = Hebp1 PE = 2 SV = 1 Isoform Tau-F of Microtubule-associated protein tau OS = Rattus norvegicus GN = Mapt Microtubule-associated protein OS = Rattus norvegicus GN = Mapt PE = 2 SV = 1 Caskin-1 OS = Rattus norvegicus GN = Caskin1 PE = 1 SV = 1 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 OS = Rattus norvegicus GN = Gnb1 PE = 1 SV = 4 Lipid phosphate phosphatase-related protein type 4 OS = Rattus norvegicus GN = Lppr4 PE = 2 SV = 1 Protein LOC688963 OS = Rattus norvegicus GN = LOC688963 PE = 2 SV = 1 Peptidyl-prolyl cis-trans isomerase F, mitochondrial OS = Rattus norvegicus GN = Ppif PE = 1 SV = 2 ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d1 OS = Rattus norvegicus GN = Atp6v0d1 PE = 2 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

EZRI_RAT

B4F7A5_RAT D3ZDF0_RAT Q6S396_RAT BIN1_RAT JAGN1_RAT LSAMP_RAT B2RYS8_RAT

GCSH_RAT ENOA_RAT THEM6_RAT D4A7L4_RAT

D3ZUX5_RAT

ERLN2_RAT D3ZUE2_RAT PSB6_RAT ARL8B_RAT NDUV2_RAT TMOD2_RAT ACBG1_RAT F1LRV4_RAT ATAD3_RAT F1LMM9_RAT RAN_RAT

F1M4A0_RAT D4A1Y0_RAT

90909.92

5.15

0

0.726

1.14242

0.75583

1.01443

0.950278

1.00122

0.910066

0.764152

0.286422

2

2

6.2

47300.3

11.02

0

0.651

1.29582

0.482277

0.958211

0.821954

1.30818

0.454887

0.912421

0.687947

1

1

3.8

39337.8

7.22

0

0.199

1.18284

0.678755

0.953985

0.804601

1.08397

0.898064

0.868126

0.548428

2

2

11.5

16588.24

4.92

2

0.481

1.16416

0.714006

1.0819

0.711623

1.21059

0.632806

1.05955

0.835568

10

6

23.6

40939.63

7.05

0

0.46

1.17179

0.699531

0.894217

0.572966

0.945612

0.775074

0.719196

0.204997

29 12

24 7

6.7 24.6

518360 49142.67

5.6 5.48

0 0

0.688 0.708

1.20178 1.15265

0.643704 0.736065

0.912704 0.963789

0.64132 0.844992

1.00549 0.957969

0.920576 0.804635

0.72261 0.850748

0.210518 0.49778

2

1

6.6

21101.74

9.8

3

0.242

1.25872

0.543249

1.18898

0.391231

1.32355

0.429674

1.31697

0.255598

16

7

22.4

39860.96

7.03

0

0.255

1.22922

0.594313

0.706556

0.119522

1.37624

0.349659

0.918938

0.709565

8

3

21.0

21958.68

5.67

0

0.705

1.34426

0.408619

0.953692

0.803403

1.29793

0.472153

1.05872

0.837915

2

2

5.2

45494.84

8.52

0

0.864

0.865441

0.607982

0.943376

0.761477

1.6865

0.07312

1.34775

0.212038

1

1

6.1

18184.53

5.8

0

0.285

1.09059

0.85824

1.03227

0.885804

1.31091

0.450347

1.12827

0.648665

27

14

35.3

47127.31

6.16

0

0.193

1.17115

0.700743

1.06646

0.764654

1.12278

0.813973

1.07319

0.797334

5

2

12.6

23747.36

9.14

1

0.001

1.46571

0.255777

1.6903

0.001685

0.628432

0.203644

1.02494

0.934167

3

2

25.8

17633.8

5.17

0

0.436

1.08714

0.865167

0.593568

0.031184

0.834073

0.52719

0.729673

0.222277

6

3

12.8

26434.31

8.25

0

1.035

1.20961

0.629443

1.11778

0.593954

1.29926

0.469892

0.994661

0.973561

1 1 1

1 1 1

3.5 0.8 4.2

37709.93 100780.7 25289.37

5.54 5.58 4.85

0 0 0

0.172 0.292 0.025

1.10984 1.11542 1.23925

0.819814 0.80877 0.576701

1.29704 1.24198 1.14191

0.177151 0.271866 0.520232

1.1289 1.33643 1.23978

0.800889 0.409194 0.576571

1.07043 1.26691 0.958355

0.805034 0.338999 0.844749

7

3

18.8

21538.78

8.67

0

0.272

1.19746

0.651637

0.957143

0.817559

1.32169

0.432691

1.18731

0.50364

7

4

28.6

27378.04

6.23

0

0.316

1.29303

0.486733

0.997216

0.985145

1.03415

0.991488

0.874652

0.568085

5

4

15.7

39491.34

5.34

0

0.68

1.1537

0.734041

0.908772

0.626498

1.03204

0.986263

1.15622

0.577849

2

2

3.9

80517.97

5.65

0

0.267

1.09853

0.842352

0.93178

0.715181

1.17169

0.711117

0.920299

0.714111

6

4

4.2

94025.38

5.13

0

0.58

1.08699

0.865453

1.17978

0.414796

1.44306

0.262804

1.49254

0.076617

6

4

7.3

66758.2

9.32

0

0.66

0.982384

0.899393

1.25652

0.244021

1.59422

0.124236

1.31286

0.261859

1

1

2.1

83311.6

6.76

0

0.28

1.21939

0.611803

0.898082

0.586969

0.61154

0.185596

0.437321

0.011391

2

1

4.6

24422.81

7.01

0

0.266

1.25109

0.556251

1.16956

0.441924

1.36036

0.372713

1.17763

0.526196

22

4

5.2

122885.2

4.73

0

0.564

1.312

0.456911

0.946956

0.775955

1.51603

0.186406

1.33068

0.235494

2

2

1.6

195367.8

6.13

0

0.908

1.17484

0.693767

0.895743

0.578476

1.39122

0.328757

0.913305

0.690866

1

1

1.3

103364.1

8.36

0

0.249

1.1357

0.768915

1.17861

0.417858

1.05638

0.9586

1.08331

0.769279

No. of Pages 73

GNAS1_RAT

4.8

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

B2GUY4_RAT

3

NSC 16186

B2GUW3_RAT

3

22 April 2015

Q6P3V9_RAT

Isoform 2 of GRIP1-associated protein 1 OS = Rattus norvegicus GN = Gripap1 60S ribosomal protein L4 OS = Rattus norvegicus GN = Rpl4 PE = 2 SV = 1 Hdac11 protein OS = Rattus norvegicus GN = Hdac11 PE = 2 SV = 1 Cd99 protein OS = Rattus norvegicus GN = Cd99 PE = 2 SV = 1 Neuroplastin OS = Rattus norvegicus GN = Nptn PE = 2 SV = 1 Plectin OS = Rattus norvegicus GN = Plec PE = 2 SV = 1 Isoform AMPH2-5 of Myc box-dependent-interacting protein 1 OS = Rattus norvegicus GN = Bin1 Protein jagunal homolog 1 OS = Rattus norvegicus GN = Jagn1 PE = 2 SV = 1 LSAMP_RAT Isoform 2 of Limbic system-associated membrane protein OS = Rattus norvegicus GN = Lsamp NADH dehydrogenase (Ubiquinone) 1 beta subcomplex 8 OS = Rattus norvegicus GN = Ndufb8 PE = 2 SV = 1 Protein Epb49 OS = Rattus norvegicus GN = Epb49 PE = 2 SV = 1 Glycine cleavage system H protein, mitochondrial OS = Rattus norvegicus GN = Gcsh PE = 2 SV = 1 Alpha-enolase OS = Rattus norvegicus GN = Eno1 PE = 1 SV = 4 Protein THEM6 OS = Rattus norvegicus GN = Them6 PE = 2 SV = 1 NADH dehydrogenase (Ubiquinone) 1 beta subcomplex, 11 (Predicted) OS = Rattus norvegicus GN = Ndufb11 PE = 4 SV = 1 Coiled-coil-helix-coiled-coil-helix domain containing 3 (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Chchd3 PE = 4 SV = 1 Erlin-2 OS = Rattus norvegicus GN = Erlin2 PE = 1 SV = 1 Coronin OS = Rattus norvegicus GN = Coro7 PE = 2 SV = 1 Proteasome subunit beta type-6 OS = Rattus norvegicus GN = Psmb6 PE = 1 SV = 3 ADP-ribosylation factor-like protein 8B OS = Rattus norvegicus GN = Arl8b PE = 2 SV = 1 NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial OS = Rattus norvegicus GN = Ndufv2 PE = 1 SV = 2 Tropomodulin-2 OS = Rattus norvegicus GN = Tmod2 PE = 1 SV = 1 Long-chain-fatty-acid–CoA ligase ACSBG1 OS = Rattus norvegicus GN = Acsbg1 PE = 1 SV = 1 Heat shock 70 kDa protein 4 OS = Rattus norvegicus GN = Hspa4 PE = 2 SV = 1 ATPase family AAA domain-containing protein 3 OS = Rattus norvegicus GN = Atad3 PE = 1 SV = 1 Elongation factor G, mitochondrial OS = Rattus norvegicus GN = Gfm1 PE = 2 SV = 1 GTP-binding nuclear protein Ran OS = Rattus norvegicus GN = Ran PE = 1 SV = 3 Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas OS = Rattus norvegicus GN = Gnas PE = 1 SV = 3 Protein Tjp1 (Fragment) OS = Rattus norvegicus GN = Tjp1 PE = 4 SV = 1 Protein Scyl2 OS = Rattus norvegicus GN = Scyl2 PE = 2 SV = 1

30

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

GRAP1_RAT

D4AAE9_RAT PDXK_RAT B5DF65_RAT D3ZLY4_RAT PHB2_RAT VATB2_RAT SYUB_RAT B1H262_RAT ACTZ_RAT B2RYJ7_RAT DHB4_RAT Q45QN0_RAT NDUF3_RAT F136A_RAT E9PTX9_RAT NAT8L_RAT Q5RK10_RAT B2GUZ6_RAT GRM7_RAT TPM3_RAT TTC19_RAT AT2B2_RAT F1MAR6_RAT PTMA_RAT

PARK7_RAT 1433F_RAT

2.0

227851.2

5.53

0

0.002

1.0952

0.849007

0.826531

0.35659

1.07277

0.922576

0.758444

0.275018

4

3

6.3

55902.7

8.18

9

0.73

1.30889

0.461718

0.919117

0.6658

0.983587

0.866776

0.635029

0.100057

1

1

0.5

229583.5

6.49

0

0.662

1.62639

0.121933

1.17996

0.414311

0.974465

0.844533

1.01556

0.961121

2

2

21.5

15292.92

9.68

0

0.096

1.32674

0.434457

0.945923

0.771771

1.05465

0.962396

0.819302

0.412851

5

4

14.1

34907.76

6.32

0

0.251

1.28539

0.499036

0.811099

0.315598

1.13896

0.779503

1.03148

0.915409

3

3

18.5

22093.99

6.29

0

0.098

1.34455

0.408198

1.19988

0.364385

0.922724

0.721197

1.03368

0.909099

1

1

2.8

68235.17

6.21

0

0.935

1.01796

0.99294

0.995211

0.976682

0.790339

0.442377

0.630066

0.095551

25 28

11 13

38.1 29.9

33311.97 56550.16

9.83 5.57

0 0

0.266 0.176

1.25111 1.19254

0.556214 0.660714

0.949372 1.31607

0.785768 0.150929

1.2769 1.24388

0.508661 0.568864

1.05388 1.54945

0.851608 0.048142

13

5

39.4

14503.99

4.48

0

0.553

1.15259

0.736178

1.00956

0.967939

1.4456

0.259831

1.25593

0.359407

5

4

8.5

89661.35

4.86

0

0.826

1.14335

0.754023

1.02186

0.923342

1.49733

0.204208

1.40932

0.141498

3

2

7.5

42613.22

6.19

0

0.285

1.08779

0.863848

1.06044

0.785671

1.50131

0.200321

1.44818

0.107287

3

2

6.7

42280.84

5.98

0

0.259

1.18574

0.673342

1.27723

0.207901

1.38363

0.339251

1.45139

0.10478

5

4

7.5

79426.83

8.77

0

0.104

1.03232

0.97619

1.20062

0.362606

1.11776

0.824767

1.15087

0.591112

36

7

24.2

40498.57

5.28

0

0.372

1.24657

0.56401

0.870395

0.490348

1.45498

0.249038

1.08668

0.760001

1

1

5.4

20696.2

7.73

0

0.282

1.02313

0.994925

0.932531

0.71815

1.24685

0.563318

0.973279

0.897396

6

3

36.2

15624.95

7.56

0

0.504

1.21742

0.615349

1.02275

0.920112

1.52854

0.175147

1.21812

0.435402

6

4

4.2

6.08

0

0.042

1.16476

0.712871

1.02371

0.916666

1.06421

0.941376

1.01592

0.960083

2

1

4.0

32718.68

8.8

0

0.029

1.12969

0.780664

0.901155

0.598214

1.21276

0.628534

0.950776

0.818262

2

2

10.3

23445.86

11.02

0

0.441

1.2272

0.597899

0.972851

0.88269

1.60801

0.115188

1.31343

0.260988

1

1

3.5

43605.27

9.3

0

0.032

1.06821

0.903305

1.21095

0.338329

0.805267

0.470415

0.957082

0.840286

1

1

1.8

8.2

0

0.096

0.931437

0.76813

0.975241

0.892683

0.896976

0.662213

0.859172

0.522017

11

8

31.5

28719.66

4.69

0

1.015

1.16304

0.716155

1.06081

0.784368

1.20926

0.635426

1.10076

0.721597

1

1

4.1

41332.95

5.88

0

0.327

0.994645

0.931545

1.28629

0.193389

0.841334

0.542033

1.32491

0.243815

41

19

18.9

5.7

8

0.166

1.12537

0.789138

0.846556

0.414554

1.36422

0.367035

0.913851

0.692672

2

2

6.2

68121.23

6.91

0

0.347

1.0848

0.86986

1.03271

0.884218

1.11161

0.838005

0.916841

0.702584

1

1

12.5

12382.13

3.75

0

1.974

1.20435

0.639005

0.681645

0.091294

1.02328

0.964552

0.559754

0.047494

7

7

7.8

5.76

1

0.397

1.14937

0.742377

0.834719

0.379644

1.15509

0.745539

0.842769

0.475389

9

5

30.7

19973.96

6.32

0

0.022

1.17284

0.697549

0.957028

0.817085

1.69545

0.069252

1.06391

0.823303

28

11

31.7

28211.42

4.81

0

0.607

1.21431

0.620937

1.10692

0.628648

1.35573

0.379619

1.29693

0.287106

130365

102230.9

136809.7

133380.3

(continued on next page)

31

No. of Pages 73

Q6PW39_RAT

4

NSC 16186

F1MAK3_RAT

6

22 April 2015

LAT1_RAT

Protein Scn2a1 OS = Rattus norvegicus GN = Scn2a1 PE = 2 SV = 1 Large neutral amino acids transporter small subunit 1 OS = Rattus norvegicus GN = Slc7a5 PE = 1 SV = 2 Protein Rics OS = Rattus norvegicus GN = Arhgap32 PE = 4 SV = 1 Protein Cisd2 OS = Rattus norvegicus GN = Cisd2 PE = 4 SV = 1 Pyridoxal kinase OS = Rattus norvegicus GN = Pdxk PE = 1 SV = 1 Biliverdin reductase B (Flavin reductase (NADPH)) OS = Rattus norvegicus GN = LOC681468 PE = 2 SV = 1 Protein Atp8b2 OS = Rattus norvegicus GN = Atp8b2 PE = 2 SV = 1 Prohibitin-2 OS = Rattus norvegicus GN = Phb2 PE = 1 SV = 1 V-type proton ATPase subunit B, brain isoform OS = Rattus norvegicus GN = Atp6v1b2 PE = 1 SV = 1 Beta-synuclein OS = Rattus norvegicus GN = Sncb PE = 1 SV = 1 Protein phosphatase 1, regulatory subunit 9B OS = Rattus norvegicus GN = Ppp1r9b PE = 2 SV = 1 Alpha-centractin OS = Rattus norvegicus GN = Actr1a PE = 1 SV = 1 ARP1 actin-related protein 1 homolog B (Yeast) OS = Rattus norvegicus GN = Actr1b PE = 2 SV = 1 Peroxisomal multifunctional enzyme type 2 OS = Rattus norvegicus GN = Hsd17b4 PE = 1 SV = 3 Guanine nucleotide binding protein alpha inhibiting 2 OS = Rattus norvegicus GN = Gnai2 PE = 2 SV = 1 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3 OS = Rattus norvegicus GN = Ndufaf3 PE = 2 SV = 1 Protein FAM136A OS = Rattus norvegicus GN = Fam136a PE = 2 SV = 1 Protein Slc12a2 OS = Rattus norvegicus GN = Slc12a2 PE = 4 SV = 1 N-acetylaspartate synthetase OS = Rattus norvegicus GN = Nat8l PE = 1 SV = 1 60S ribosomal protein L13a OS = Rattus norvegicus GN = Rpl13a PE = 2 SV = 1 Protein Rtn4ip1 OS = Rattus norvegicus GN = Rtn4ip1 PE = 2 SV = 1 Metabotropic glutamate receptor 7 OS = Rattus norvegicus GN = Grm7 PE = 1 SV = 1 Isoform 2 of Tropomyosin alpha-3 chain OS = Rattus norvegicus GN = Tpm3 Tetratricopeptide repeat protein 19, mitochondrial OS = Rattus norvegicus GN = Ttc19 PE = 2 SV = 1 Plasma membrane calcium-transporting ATPase 2 OS = Rattus norvegicus GN = Atp2b2 PE = 2 SV = 2 Protein Prodh OS = Rattus norvegicus GN = Prodh PE = 4 SV = 1 Prothymosin alpha OS = Rattus norvegicus GN = Ptma PE = 1 SV = 2 Neuronal cell adhesion molecule long isoform Nc1 OS = Rattus norvegicus GN = Nrcam PE = 2 SV = 1 Protein DJ-1 OS = Rattus norvegicus GN = Park7 PE = 1 SV = 1 14-3-3 protein eta OS = Rattus norvegicus GN = Ywhah PE = 1 SV = 2

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

SCN2A_RAT

F1M5C5_RAT HIBCH_RAT F1M953_RAT F1M8H6_RAT SAM50_RAT RTCB_RAT VTI1B_RAT

NFS1_RAT CRYM_RAT MOBP_RAT F1LRL9_RAT 4F2_RAT 1433Z_RAT ODO1_RAT CAPZB_RAT D3ZHX3_RAT F1M8Z9_RAT AP1M1_RAT AGAP2_RAT Q76GL9_RAT TCPG_RAT O88321_RAT

PSA3_RAT Q63555_RAT 5HT1A_RAT

24787.84

5.21

0

0.381

1.10883

0.821825

1.00486

0.985006

1.13281

0.792561

1.08152

0.77423

8

5

10.0

83058.77

6.22

1

0.413

0.808221

0.482627

1.07664

0.729548

1.32998

0.419374

1.02659

0.929443

4

3

30.5

18095.44

8.58

1

0.163

1.01267

0.979003

0.930957

0.711933

1.39969

0.317311

1.00241

0.998985

1

1

4.0

22780.89

4.85

0

0.396

1.19706

0.652363

1.00592

0.981152

1.27079

0.519555

0.964826

0.867507

3

2

7.0

43024.17

8.64

0

0.231

1.17469

0.694051

1.10576

0.632397

1.21173

0.630566

1.04735

0.870126

32

14

28.4

73743.69

5.87

0

0.414

1.14658

0.747763

1.50266

0.02225

1.01228

0.93734

1.1801

0.520395

3

3

6.3

75612.14

5.86

0

0.454

1.13203

0.776083

0.96605

0.854366

1.23187

0.591577

1.04442

0.878451

10

6

12.8

51959.58

6.34

0

0.189

1.16616

0.710216

0.90231

0.602463

1.29393

0.478985

0.931288

0.751165

2

2

5.9

55248.73

6.77

0

0.241

1.11105

0.817431

1.07148

0.747288

0.935201

0.750414

0.83521

0.454696

1

1

5.6

26703.15

9.04

1

0.606

1.14856

0.743946

1.27039

0.219369

0.876076

0.61581

0.92358

0.725108

1

1

0.9

174330.3

6.28

0

0.313

1.212

0.62511

1.01718

0.940304

0.888909

0.644137

0.803817

0.374394

1

1

3.1

50012

8.92

0

0.222

1.19259

0.660621

1.23376

0.28852

1.30989

0.452036

0.993182

0.968277

4

2

5.1

33553.86

5.34

0

0.05

1.1008

0.837815

1.10503

0.634752

1.3673

0.362524

1.20639

0.460728

1

1

6.5

18916.74

11.04

0

1.22

1.17628

0.691053

0.566929

0.021694

1.24658

0.563824

0.599171

0.071036

29

15

8.8

4.74

0

0.849

1.08034

0.878837

0.796805

0.280504

1.38271

0.340524

1.04584

0.874416

5

4

7.0

58071.49

5.19

1

0.126

1.09981

0.839786

0.948685

0.782974

1.23743

0.581001

0.989271

0.954312

32

11

31.4

27770.83

4.73

0

0.635

1.15054

0.740121

1.03769

0.866318

1.34456

0.396567

1.08369

0.768234

15

10

13.5

117741.4

6.55

0

0.319

1.03018

0.980558

1.24789

0.260296

0.898579

0.665831

0.912705

0.688886

3

3

18.4

30628.4

5.69

0

0.554

1.07408

0.891457

1.32273

0.142492

1.07283

0.922457

1.24516

0.380159

2

2

16.1

22497.7

8.98

0

0.412

0.905153

0.702687

0.864421

0.470682

1.32999

0.419359

1.08127

0.774911

3

3

7.0

61913.11

5.37

0

0.1

1.0716

0.896469

1.83639

0.000141

1.10156

0.859753

0.718813

0.204386

1

1

3.8

48556.29

6.82

0

0.277

1.11058

0.81836

1.04721

0.83237

0.917506

0.709095

0.975304

0.904582

2

2

2.3

9.89

0

0.425

1.15521

0.731141

1.16282

0.460364

0.97083

0.835704

1.02726

0.927515

5

3

6.6

56137.88

6.38

10

0.529

1.08625

0.866948

0.550614

0.017218

1.32225

0.431773

0.618312

0.085527

7

6

12.3

60646.34

6.23

0

0.271

1.11993

0.799846

1.0132

0.954737

0.845469

0.550579

0.774694

0.308314

2

2

9.0

39335.03

5.06

0

0.271

1.18636

0.67218

0.939631

0.746424

0.825637

0.510209

0.666832

0.133079

1

1

3.7

38829.93

5.7

0

0.774

1.00023

0.946238

0.892557

0.567002

0.972222

0.839083

0.677744

0.146175

2

2

9.0

28418.93

5.29

0

0.283

1.12751

0.784942

1.41006

0.062277

1.18093

0.692192

1.43984

0.114012

2 1

2 1

3.8 3.6

87747.5 46428.66

5.92 9.16

0 7

0.929 0.182

0.966426 1.12552

0.857801 0.788838

0.73432 0.784732

0.158582 0.253005

1.17013 0.789651

0.71432 0.441109

0.690439 0.620375

0.162626 0.087222

269639.6

124436.1

No. of Pages 73

NHRF1_RAT

24.6

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

D4AEH9_RAT

4

NSC 16186

Q6LBV1_RAT

8

22 April 2015

LETM1_RAT

Ubiquitin carboxyl-terminal hydrolase isozyme L1 (Fragment) OS = Rattus norvegicus GN = Uchl1 PE = 2 SV = 1 LETM1 and EF-hand domain-containing protein 1, mitochondrial OS = Rattus norvegicus GN = Letm1 PE = 1 SV = 1 Rat myelin-associated glycoprotein (S-MAG) C-term OS = Rattus norvegicus GN = Mag PE = 2 SV = 1 Uncharacterized protein (Fragment) OS = Rattus norvegicus PE = 4 SV = 1 3-hydroxyisobutyryl-CoA hydrolase, mitochondrial OS = Rattus norvegicus GN = Hibch PE = 1 SV = 2 Stress-70 protein, mitochondrial OS = Rattus norvegicus GN = Hspa9 PE = 2 SV = 1 Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma OS = Rattus norvegicus GN = Pip5k1c PE = 2 SV = 1 Sorting and assembly machinery component 50 homolog OS = Rattus norvegicus GN = Samm50 PE = 1 SV = 1 tRNA-splicing ligase RtcB homolog OS = Rattus norvegicus PE = 2 SV = 1 Vesicle transport through interaction with t-SNAREs homolog 1B OS = Rattus norvegicus GN = Vti1b PE = 1 SV = 2 Amylo-1, 6-glucosidase, 4-alpha-glucanotransferase (Glycogen debranching enzyme, glycogen storage disease type III) (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Agl PE = 4 SV = 1 Cysteine desulfurase, mitochondrial OS = Rattus norvegicus GN = Nfs1 PE = 2 SV = 1 Thiomorpholine-carboxylate dehydrogenase OS = Rattus norvegicus GN = Crym PE = 1 SV = 1 Isoform 2 of Myelin-associated oligodendrocyte basic protein OS = Rattus norvegicus GN = Mobp Microtubule-associated protein 1B OS = Rattus norvegicus GN = Map1b PE = 2 SV = 1 4F2 cell-surface antigen heavy chain OS = Rattus norvegicus GN = Slc3a2 PE = 1 SV = 1 14-3-3 protein zeta/delta OS = Rattus norvegicus GN = Ywhaz PE = 1 SV = 1 2-oxoglutarate dehydrogenase, mitochondrial OS = Rattus norvegicus GN = Ogdh PE = 2 SV = 1 F-actin-capping protein subunit beta OS = Rattus norvegicus GN = Capzb PE = 1 SV = 1 Protein Diras2 OS = Rattus norvegicus GN = Diras2 PE = 4 SV = 1 Protein Rap1gds1 (Fragment) OS = Rattus norvegicus GN = Rap1gds1 PE = 2 SV = 1 AP-1 complex subunit mu-1 OS = Rattus norvegicus GN = Ap1m1 PE = 1 SV = 3 Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 OS = Rattus norvegicus GN = Agap2 PE = 1 SV = 1 Amino acid transporter OS = Rattus norvegicus GN = Slc1a4 PE = 2 SV = 1 T-complex protein 1 subunit gamma OS = Rattus norvegicus GN = Cct3 PE = 1 SV = 1 Protein Psmd4 OS = Rattus norvegicus GN = Psmd4 PE = 2 SV = 1 Na(+)/H(+) exchange regulatory cofactor NHE-RF1 OS = Rattus norvegicus GN = Slc9a3r1 PE = 1 SV = 3 Proteasome subunit alpha type-3 OS = Rattus norvegicus GN = Psma3 PE = 1 SV = 3 SP120 OS = Rattus norvegicus GN = Hnrnpu PE = 2 SV = 1 5-hydroxytryptamine receptor 1A OS = Rattus norvegicus GN = Htr1a PE = 3 SV = 1

32

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

UCHL1_RAT

PTPM1_RAT

Q6IMX4_RAT LRFN1_RAT SYSC_RAT WASF1_RAT MAP1S_RAT F1LW39_RAT KC1G2_RAT F1M4D1_RAT F1LM47_RAT D3ZKD9_RAT F1LYA6_RAT D4A5I9_RAT F1M7N2_RAT SET_RAT COX7C_RAT BSCL2_RAT D3ZAX3_RAT 1433G_RAT VIAAT_RAT F1MAL3_RAT ETBR2_RAT F1LMY3_RAT Q06C60_RAT

RAB1A_RAT TRIM2_RAT GDIB_RAT

Protein Sec23a OS = Rattus norvegicus GN = Sec23a PE = 2 SV = 1 Ras-related protein Rab-1A OS = Rattus norvegicus GN = Rab1A PE = 1 SV = 3 Tripartite motif-containing protein 2 OS = Rattus norvegicus GN = Trim2 PE = 1 SV = 2 Rab GDP dissociation inhibitor beta OS = Rattus norvegicus GN = Gdi2 PE = 1 SV = 2

8.4

67000.71

8.25

12

0.468

1.12561

0.788667

0.611279

0.039304

1.12629

0.806474

0.688171

0.159588

2

2

5.4

36407.44

9.03

0

0.113

1.08594

0.867561

0.969139

0.867212

1.00423

0.917463

0.791999

0.346589

2

2

12.4

24476.97

6.07

0

0.102

1.15293

0.735512

0.768622

0.219322

1.34576

0.394728

1.03874

0.894639

1

1

6.7

21886.11

9.63

0

0.117

0.945317

0.803404

1.79232

0.000312

0.791481

0.444487

1.37587

0.177188

7

3

11.9

35232.81

9.25

6

0.144

1.10643

0.826595

0.873677

0.501338

1.25021

0.557068

1.13696

0.626264

2

2

3.9

81968.58

7.89

0

0.097

1.30228

0.472061

0.957133

0.817518

1.33718

0.408029

1

0.992644

2

2

5.3

58587.25

5.86

0

0.525

1.21591

0.618055

1.1892

0.390677

0.861023

0.583303

0.946854

0.804633

2

2

4.7

61514.27

5.94

0

0.622

1.12031

0.799103

0.996284

0.98121

0.928745

0.73525

0.805718

0.378993

2

2

2.8

6.68

0

0.284

1.04262

0.955233

1.07514

0.734703

1.34442

0.396784

0.921695

0.718782

2

2

5.6

72935.11

6.46

0

0.612

1.1003

0.838809

1.34247

0.119596

0.907665

0.686471

0.875878

0.571815

1

1

2.0

50129.61

9.1

0

0.62

0.993269

0.92793

1.47244

0.031678

0.891398

0.649691

1.21091

0.450878

9

4

17.5

23209.38

8.87

0

0.069

1.11584

0.807935

1.20385

0.354903

1.09135

0.88195

1.25312

0.364754

102804.7

25

12

23.3

47286.13

6.08

0

0.026

1.13768

0.765058

1.35867

0.103039

1.50252

0.199143

1.80977

0.003547

10

8

26.3

37954.36

9.98

0

0.833

1.12402

0.791805

1.05558

0.802735

1.20374

0.646325

1.03435

0.907198

2

2

5.8

49143.3

5.93

0

0.542

0.728346

0.334

1.14011

0.52555

1.05539

0.960773

0.796597

0.357246

6

5

6.1

145663.9

8.64

0

0.607

1.2054

0.6371

1.06241

0.778793

1.07636

0.914711

1.11161

0.692477

1

1

4.2

60018.11

7.15

0

0.018

1.45371

0.268813

1.11039

0.617463

0.849484

0.558939

0.797593

0.359584

1 6

1 1

3.5 14.3

33405.41 7374.62

4.22 11

0 0

1.28 0.114

1.01215 1.04196

0.977616 0.956575

0.891614 0.918507

0.563626 0.663455

1.83202 1.27575

0.028241 0.5107

1.72551 1.05335

0.009009 0.853088

1 46

1 26

2.4 22.6

42408.55 130647.5

5.71 5.69

2 0

0.162 0.193

0.801271 1.12555

0.468419 0.788792

1.3123 0.884376

0.155871 0.538048

1.25673 1.25993

0.545032 0.539188

1.14592 0.877768

0.603528 0.577587

40

14

36.0

28302.27

4.8

0

0.68

1.12206

0.795659

1.03161

0.888162

1.28744

0.490177

1.17499

0.532441

8

3

8.8

57406.52

6.19

9

0.464

1.08532

0.86881

1.03251

0.88491

1.29835

0.471432

0.987451

0.947816

9 1

8 1

4.6 2.1

267950.9 52859.15

5.28 6.97

0 4

0.651 0.24

1.29256 1.04516

0.487475 0.950065

1.68277 1.0273

0.001894 0.903678

0.704423 1.36845

0.300608 0.36085

1.02394 1.34821

0.937041 0.211441

4

4

2.3

255368.2

4.74

0

0.42

1.05768

0.924638

1.06986

0.752877

1.57472

0.137973

1.35274

0.205516

2

1

11.0

14403.31

9.41

0

0.191

0.731587

0.339386

1.14432

0.513128

0.928137

0.733825

0.716936

0.201402

1

1

2.2

86160.82

6.64

0

0.235

1.3562

0.391548

1.17185

0.435765

1.20097

0.651826

1.32519

0.24341

11

3

15.6

22677.49

5.93

0

0.294

1.08477

0.869926

1.3042

0.166918

1.4539

0.250257

1.21622

0.439434

8

6

9.3

81426.22

6.61

0

0.328

1.00332

0.954374

1.01903

0.933597

1.06205

0.94612

0.944772

0.797421

6

4

13.9

50536.56

5.93

0

0.304

0.796517

0.458834

1.60071

0.006282

0.76158

0.391146

1.11311

0.688499

33

(continued on next page)

No. of Pages 73

B5DFC3_RAT

2

NSC 16186

HPRT_RAT

3

22 April 2015

D3ZFR9_RAT

Sodium- and chloride-dependent GABA transporter 1 OS = Rattus norvegicus GN = Slc6a1 PE = 1 SV = 1 Protein Rdh13 OS = Rattus norvegicus GN = Rdh13 PE = 3 SV = 1 Hypoxanthine-guanine phosphoribosyltransferase OS = Rattus norvegicus GN = Hprt1 PE = 1 SV = 1 Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 OS = Rattus norvegicus GN = Ptpmt1 PE = 2 SV = 1 Lipid phosphate phosphohydrolase 3 OS = Rattus norvegicus GN = Ppap2b PE = 2 SV = 1 Leucine-rich repeat and fibronectin type III domain-containing protein 1 OS = Rattus norvegicus GN = Lrfn1 PE = 1 SV = 1 Serine–tRNA ligase, cytoplasmic OS = Rattus norvegicus GN = Sars PE = 1 SV = 3 Wiskott-Aldrich syndrome protein family member 1 OS = Rattus norvegicus GN = Wasf1 PE = 2 SV = 1 Microtubule-associated protein 1S OS = Rattus norvegicus GN = Map1s PE = 1 SV = 1 Protein Srgap3 (Fragment) OS = Rattus norvegicus GN = Srgap3 PE = 2 SV = 1 Casein kinase 1, gamma 2, isoform CRA_a OS = Rattus norvegicus GN = Csnk1g2 PE = 3 SV = 1 Glyceraldehyde-3-phosphate dehydrogenase (Fragment) OS = Rattus norvegicus PE = 3 SV = 1 Protein Sucla2 (Fragment) OS = Rattus norvegicus GN = Sucla2 PE = 2 SV = 1 Microtubule-associated protein OS = Rattus norvegicus GN = Mapt PE = 2 SV = 1 Protein Abi2 (Fragment) OS = Rattus norvegicus GN = Abi2 PE = 2 SV = 1 Protein Myo6 OS = Rattus norvegicus GN = Myo6 PE = 2 SV = 1 Ectonucleoside triphosphate diphosphohydrolase 2 OS = Rattus norvegicus GN = Entpd2 PE = 2 SV = 1 Protein SET OS = Rattus norvegicus GN = Set PE = 1 SV = 2 Cytochrome c oxidase subunit 7C, mitochondrial OS = Rattus norvegicus GN = Cox7c PE = 1 SV = 2 Seipin OS = Rattus norvegicus GN = Bscl2 PE = 2 SV = 1 Plasma membrane calcium-transporting ATPase 1 OS = Rattus norvegicus GN = Atp2b1 PE = 2 SV = 1 14-3-3 protein gamma OS = Rattus norvegicus GN = Ywhag PE = 1 SV = 2 Vesicular inhibitory amino acid transporter OS = Rattus norvegicus GN = Slc32a1 PE = 1 SV = 1 Protein Sptb OS = Rattus norvegicus GN = Sptb PE = 4 SV = 1 Endothelin B receptor-like protein 2 OS = Rattus norvegicus GN = Gpr37l1 PE = 2 SV = 1 Receptor-type tyrosine-protein phosphatase zeta OS = Rattus norvegicus GN = Ptprz1 PE = 2 SV = 1 BolA-like 1 (E. coli) (Predicted) OS = Rattus norvegicus GN = Bola1 PE = 2 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

SC6A1_RAT

PHB_RAT BASP1_RAT TIM10_RAT SYN1_RAT ATPB_RAT B2RYS2_RAT TPM2_RAT F1LNY1_RAT

CALR_RAT CH10_RAT PRDX1_RAT DHE3_RAT D3ZEA1_RAT F1M542_RAT D4A0I5_RAT CAN2_RAT ADRO_RAT F1LP27_RAT KACB_RAT PGAM1_RAT NUP98_RAT COX5B_RAT AT2B3_RAT DCLK2_RAT

PYC_RAT GRIA1_RAT

49031.73

4.87

1

0.225

1.07282

0.894

1.0561

0.800899

0.788325

0.43867

0.897406

0.639126

1

1

4.5

34576.68

6.06

0

0.175

1.03272

0.975384

1.32982

0.133901

0.841027

0.541402

0.973556

0.898378

2

2

7.1

33473.07

10.78

0

0.803

1.2303

0.592404

1.08771

0.692008

1.26699

0.526384

0.999466

0.990735

19 26

7 10

27.2 64.6

29819.71 21790.01

5.57 4.5

0 0

0.009 1.137

1.15836 1.10738

0.725097 0.824712

0.960325 0.888737

0.830666 0.553389

1.41773 1.25885

0.293801 0.541166

1.12753 1.14607

0.650576 0.603142

5

3

38.9

10332.88

5.89

0

0.649

1.27106

0.522554

0.852659

0.433269

0.98346

0.866466

0.804609

0.376306

74

19

33.4

73987.49

9.81

0

0.575

1.1268

0.786337

1.0113

0.961623

1.05661

0.958095

0.907477

0.671717

284

24

50.9

56352.87

5.18

0

0.034

1.14297

0.754761

1.09402

0.670918

1.02842

0.977291

1.00114

0.996723

8

3

26.1

13558.39

9.3

0

1.05

1.0678

0.904146

1.21787

0.322681

1.27646

0.509449

1.3221

0.247947

6

5

16.2

32740.27

4.62

0

1.067

1.11777

0.804124

0.916629

0.656258

1.38203

0.341481

1.31281

0.261939

4

3

3.3

7.33

0

0.808

1.07059

0.898501

0.87658

0.511166

1.75133

0.048714

1.31482

0.25886

42

6

20.4

35201.17

8.83

1

0.548

1.10674

0.82599

0.791762

0.268779

1.28068

0.501994

0.937194

0.771329

11 18

5 8

14.4 58.8

47994.87 10901.53

4.33 8.89

0 0

1.099 0.037

1.08131 1.16843

0.87689 0.705901

1.14783 1.06569

0.502882 0.767347

1.1469 1.30868

0.762719 0.45405

1.29908 1.47745

0.283605 0.086129

11

8

34.7

22109.14

8.27

0

0.222

1.26093

0.539511

1.57432

0.008989

1.07036

0.927867

1.2538

0.363457

96

22

40.3

61415.21

8.05

0

0.306

1.10091

0.837599

1.12395

0.574658

1.08485

0.896132

1.0965

0.733136

2

2

5.9

48317.48

9.5

0

0.961

1.04469

0.951031

1.19156

0.384763

0.945748

0.775397

1.0121

0.971075

1

1

8.2

21947.1

8.85

0

0.458

0.920748

0.741286

0.612358

0.039852

1.52089

0.181969

0.987068

0.94645

4

3

4.6

99828.28

6.67

0

0.533

1.10551

0.828423

0.949281

0.785399

1.38177

0.341849

1.06563

0.818477

2

1

2.6

79918.4

4.86

0

0.407

1.15553

0.730514

0.958178

0.821817

0.950318

0.786296

0.838729

0.464266

3

2

3.5

54260.77

9.35

0

0.236

1.10114

0.837134

1.10611

0.631251

0.786922

0.436096

0.883502

0.595265

1

1

4.8

36302.8

6.98

0

0.184

1.27561

0.515017

1.16333

0.458943

0.93854

0.758298

0.997332

0.983109

6

3

35.9

11600.7

4.97

0

0.453

1.10621

0.827032

1.20138

0.360795

1.35542

0.380075

1.37095

0.182953

18

10

46.1

28831.64

6.67

0

0.488

1.03391

0.972964

0.978822

0.907683

1.15729

0.740945

1.06384

0.823516

1

1

0.4

5.83

0

0.413

0.797387

0.46058

0.565604

0.021296

1.52517

0.178134

1.36537

0.189669

19

4

31.8

7.68

0

0.281

1.08129

0.876919

0.987295

0.9433

1.16912

0.716408

0.984492

0.937265

26

12

12.1

5.76

0

0.089

1.09519

0.849023

0.671387

0.081351

1.25267

0.552508

0.810372

0.390396

3

2

6.5

40381.96

9.85

0

0.593

1.12308

0.793653

1.04065

0.855734

1.14781

0.760812

0.872068

0.560259

53

15

37.3

45085.75

8.03

0

0.311

1.08825

0.86294

1.02414

0.915109

1.12567

0.807788

1.15654

0.577053

18

10

11.2

129775.3

6.34

0

0.165

1.05539

0.929279

0.924759

0.687639

1.12587

0.807375

1.02654

0.92958

16

12

17.4

101577.9

7.46

0

0.194

1.09314

0.853125

0.845887

0.412529

1.11679

0.826847

1.0148

0.963297

146895.4

197280.4 13914.79 128293.3

No. of Pages 73

ALDOA_RAT

3.1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

AT1B1_RAT

1

NSC 16186

Q6P790_RAT

2

22 April 2015

Q4V8E2_RAT

Protein tweety homolog 1 OS = Rattus norvegicus GN = Ttyh1 PE = 2 SV = 1 Proteasome (Prosome, macropain) 26S subunit, non-ATPase, 14 OS = Rattus norvegicus GN = Psmd14 PE = 2 SV = 1 60S ribosomal protein L6 (Fragment) OS = Rattus norvegicus GN = Rpl6 PE = 2 SV = 1 Prohibitin OS = Rattus norvegicus GN = Phb PE = 1 SV = 1 Brain acid soluble protein 1 OS = Rattus norvegicus GN = Basp1 PE = 1 SV = 2 Mitochondrial import inner membrane translocase subunit Tim10 OS = Rattus norvegicus GN = Timm10 PE = 3 SV = 1 Synapsin-1 OS = Rattus norvegicus GN = Syn1 PE = 1 SV = 3 ATP synthase subunit beta, mitochondrial OS = Rattus norvegicus GN = Atp5b PE = 1 SV = 2 Cytochrome b-c1 complex subunit 7 OS = Rattus norvegicus GN = Uqcrb PE = 3 SV = 1 Tropomyosin beta chain OS = Rattus norvegicus GN = Tpm2 PE = 2 SV = 1 Misshapen-like kinase 1 (Fragment) OS = Rattus norvegicus GN = LOC687705 PE = 2 SV = 1 Sodium/potassium-transporting ATPase subunit beta-1 OS = Rattus norvegicus GN = Atp1b1 PE = 1 SV = 1 Calreticulin OS = Rattus norvegicus GN = Calr PE = 1 SV = 1 10 kDa heat shock protein, mitochondrial OS = Rattus norvegicus GN = Hspe1 PE = 1 SV = 3 Peroxiredoxin-1 OS = Rattus norvegicus GN = Prdx1 PE = 1 SV = 1 Glutamate dehydrogenase 1, mitochondrial OS = Rattus norvegicus GN = Glud1 PE = 1 SV = 2 Protein RGD1310819 OS = Rattus norvegicus GN = RGD1310819 PE = 2 SV = 1 Protein Adam22 (Fragment) OS = Rattus norvegicus GN = Adam22 PE = 4 SV = 1 Protein Dnajc6 OS = Rattus norvegicus GN = Dnajc6 PE = 2 SV = 1 Calpain-2 catalytic subunit OS = Rattus norvegicus GN = Capn2 PE = 1 SV = 3 NADPH:adrenodoxin oxidoreductase, mitochondrial OS = Rattus norvegicus GN = Fdxr PE = 3 SV = 1 Eukaryotic initiation factor 4A-II OS = Rattus norvegicus GN = Eif4a2 PE = 2 SV = 1 Ig kappa chain C region, B allele OS = Rattus norvegicus PE = 1 SV = 1 Phosphoglycerate mutase 1 OS = Rattus norvegicus GN = Pgam1 PE = 1 SV = 4 Nuclear pore complex protein Nup98-Nup96 OS = Rattus norvegicus GN = Nup98 PE = 1 SV = 2 Cytochrome c oxidase subunit 5B, mitochondrial OS = Rattus norvegicus GN = Cox5b PE = 1 SV = 2 Isoform XE of Plasma membrane calcium-transporting ATPase 3 OS = Rattus norvegicus GN = Atp2b3 Serine/threonine-protein kinase DCLK2 OS = Rattus norvegicus GN = Dclk2 PE = 4 SV = 1 Fructose-bisphosphate aldolase OS = Rattus norvegicus GN = Aldoa PE = 3 SV = 1 Pyruvate carboxylase, mitochondrial OS = Rattus norvegicus GN = Pc PE = 1 SV = 2 Glutamate receptor 1 OS = Rattus norvegicus GN = Gria1 PE = 1 SV = 2

34

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

TTYH1_RAT

GPDA_RAT F1MA36_RAT THOP1_RAT MPCP_RAT DOPD_RAT GNAO_RAT SYUA_RAT VAPB_RAT Q9JJ10_RAT RGRF2_RAT NCDN_RAT Q6LDS4_RAT MDHC_RAT OPA1_RAT TMM11_RAT D4ACB6_RAT E9PSZ3_RAT B0BMY7_RAT

G3V928_RAT G3V8T7_RAT 1433B_RAT COX5A_RAT CSDE1_RAT

AT2B4_RAT CAZA2_RAT

16.6

40417.04

5.59

0

0.255

1.07705

0.885458

0.921156

0.673661

1.25484

0.548504

1.07861

0.782275

3

3

5.9

82924.21

6.58

0

0.26

1.13628

0.767774

1.00873

0.970933

0.802377

0.464912

0.803934

0.374677

1

1

11.1

15006.21

10.17

0

0.537

1.20631

0.635434

0.992168

0.963843

1.07893

0.909079

0.984893

0.938695

4

3

10.9

37452.12

6.16

0

0.134

1.17454

0.694348

1.15373

0.485914

1.00403

0.916973

1.22679

0.417195

52

32

19.1

5.59

0

0.643

1.12376

0.792316

0.963555

0.844021

1.06395

0.941936

0.861972

0.530207

2

2

3.2

78384.59

5.64

0

0.435

1.0172

0.990955

0.85119

0.428718

1.19797

0.657809

0.9351

0.764162

31

10

20.2

39444.68

9.41

0

0.062

1.10844

0.822598

1.03094

0.89059

1.26873

0.523249

1.07086

0.803846

6

3

39.0

13133.12

6.09

0

0.044

1.13981

0.760902

0.966388

0.855769

0.902894

0.675603

0.891013

0.61879

77

12

33.1

40080.1

5.69

0

0.347

1.13676

0.766833

0.861003

0.459629

1.2566

0.545275

0.969986

0.885733

18

8

48.6

14515.09

4.74

0

-0.415

1.0837

0.87208

0.987501

0.944171

1.36096

0.371825

1.19026

0.496871

2

1

5.8

26915.89

7.64

1

0.316

1.12422

0.791404

1.14017

0.52539

0.709405

0.307894

0.853449

0.505486

3

1

2.4

60726.12

7.95

0

0.485

0.897773

0.684676

0.867038

0.479244

1.91856

0.014977

1.5668

0.041475

270936.9

3

3

3.1

8.03

0

0.381

1.17149

0.700096

0.921604

0.675392

0.890587

0.647879

0.945954

0.801513

7

4

6.7

78922.53

5.44

0

0.132

1.07683

0.885909

0.963033

0.84186

1.14608

0.764459

0.983038

0.932083

18

8

53.3

15709.21

5.88

0

0.434

1.04149

0.957531

0.938487

0.741845

1.1333

0.791504

1.0784

0.78285

7

5

16.5

36482.68

6.16

0

0.059

1.07349

0.892638

1.1988

0.366994

0.94023

0.762297

1.03445

0.906896

35

18

21.4

6.89

0

0.579

1.13829

0.76386

1.16504

0.454249

1.03983

0.995034

1.36858

0.185776

1

1

8.4

21341.32

6.98

0

0.004

1.08077

0.877974

0.636827

0.054131

2.03497

0.00588

1.52438

0.059348

1

1

1.3

84554.28

5.05

0

0.575

1.10923

0.821039

0.938185

0.740639

0.951833

0.789918

0.899348

0.645358

155

77

33.4

5.24

0

0.794

1.07995

0.879625

1.00598

0.980941

1.11654

0.827374

0.949348

0.813292

2

2

10.0

6.33

0

0.482

1.12681

0.786309

1.04625

0.835754

1.45656

0.247243

1.2027

0.468854

12

8

2.5

5.14

0

0.507

1.1601

0.72176

0.988161

0.94695

1.01099

0.934166

0.972572

0.894891

2

2

4.5

62011.15

4.88

0

0.39

1.14657

0.747793

1.35857

0.103138

1.28811

0.489018

1.26903

0.335164

36

10

28.5

28054.07

4.81

0

0.681

1.08158

0.876344

1.16878

0.444032

1.24271

0.571066

1.291

0.2969

12

4

17.8

16129.34

6.08

0

0.142

1.01224

0.97786

0.863506

0.46771

1.45671

0.247076

1.27764

0.31981

2

2

2.9

88893.61

5.97

0

0.448

1.10689

0.82569

0.969587

0.869076

1.11187

0.837438

0.964358

0.865857

3

3

14.8

23438.61

6.89

0

0.22

1.03072

0.979448

1.15901

0.470967

0.652604

0.231645

0.691347

0.163855

22

9

9.4

6.92

0

0.083

1.04206

0.95637

0.746862

0.179114

1.37185

0.355946

0.825513

0.428911

8

4

19.9

5.57

0

0.586

0.988661

0.915837

1.06517

0.769155

0.830391

0.519742

0.737094

0.235132

135825.3

117391.6

285036.7 39472.45

504884.5

128655.1 32966.65

(continued on next page)

35

No. of Pages 73

B6DYQ7_RAT

4

NSC 16186

D4AA84_RAT

6

22 April 2015

D3ZKG1_RAT

Cell adhesion molecule 4 (Fragment) OS = Rattus norvegicus GN = Cadm4 PE = 2 SV = 1 Protein LOC100361295 OS = Rattus norvegicus GN = LOC100361295 PE = 4 SV = 1 Protein Cisd3 OS = Rattus norvegicus GN = Cisd3 PE = 2 SV = 1 Glycerol-3-phosphate dehydrogenase [NAD(+)], cytoplasmic OS = Rattus norvegicus GN = Gpd1 PE = 1 SV = 4 Spectrin beta chain, non-erythrocytic 2 OS = Rattus norvegicus GN = Sptbn2 PE = 2 SV = 1 Thimet oligopeptidase OS = Rattus norvegicus GN = Thop1 PE = 1 SV = 4 Phosphate carrier protein, mitochondrial OS = Rattus norvegicus GN = Slc25a3 PE = 1 SV = 1 D-dopachrome decarboxylase OS = Rattus norvegicus GN = Ddt PE = 1 SV = 3 Isoform Alpha-2 of Guanine nucleotide-binding protein G(o) subunit alpha OS = Rattus norvegicus GN = Gnao1 Alpha-synuclein OS = Rattus norvegicus GN = Snca PE = 1 SV = 1 Vesicle-associated membrane protein-associated protein B OS = Rattus norvegicus GN = Vapb PE = 1 SV = 3 Neuronal C-SRC tyrosine-specific protein kinase OS = Rattus norvegicus GN = Src PE = 2 SV = 1 Ras-specific guanine nucleotide-releasing factor 2 OS = Rattus norvegicus GN = Rasgrf2 PE = 1 SV = 1 Neurochondrin OS = Rattus norvegicus GN = Ncdn PE = 1 SV = 2 Superoxide dismutase [Cu-Zn] OS = Rattus norvegicus GN = Sod1 PE = 2 SV = 1 Malate dehydrogenase, cytoplasmic OS = Rattus norvegicus GN = Mdh1 PE = 1 SV = 3 Isoform 2 of Dynamin-like 120 kDa protein, mitochondrial OS = Rattus norvegicus GN = Opa1 Transmembrane protein 11, mitochondrial OS = Rattus norvegicus GN = Tmem11 PE = 2 SV = 1 Pleckstrin and Sec7 domain containing 2 (Predicted) OS = Rattus norvegicus GN = Psd2 PE = 4 SV = 1 Spectrin alpha chain, non-erythrocytic 1 OS = Rattus norvegicus GN = Sptan1 PE = 2 SV = 1 Protein tyrosine kinase 9-like (A6-related protein) (Predicted), isoform CRA_b OS = Rattus norvegicus GN = LOC684352 PE = 2 SV = 1 Protein Lrp1 OS = Rattus norvegicus GN = Lrp1 PE = 4 SV = 1 Protein Tdrkh OS = Rattus norvegicus GN = Tdrkh PE = 4 SV = 1 14-3-3 protein beta/alpha OS = Rattus norvegicus GN = Ywhab PE = 1 SV = 3 Cytochrome c oxidase subunit 5A, mitochondrial OS = Rattus norvegicus GN = Cox5a PE = 1 SV = 1 Cold shock domain-containing protein E1 OS = Rattus norvegicus GN = Csde1 PE = 2 SV = 1 Glutathione S-transferase pi OS = Rattus norvegicus GN = Gstp1 PE = 2 SV = 1 Plasma membrane calcium-transporting ATPase 4 OS = Rattus norvegicus GN = Atp2b4 PE = 2 SV = 1 F-actin-capping protein subunit alpha-2 OS = Rattus norvegicus GN = Capza2 PE = 1 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

F1M7V6_RAT

I7EFB0_RAT F1LRT9_RAT DYHC1_RAT NSF_RAT Q6P9V1_RAT Q5BJZ3_RAT ABCF1_RAT

D4A520_RAT G3V6S0_RAT D4A831_RAT D4A4G9_RAT F1M7K7_RAT

ACOT2_RAT B1AC44_RAT EXOC3_RAT 1433T_RAT AATM_RAT CN37_RAT DLG4_RAT AASD1_RAT GPR37_RAT D3ZXR8_RAT

SERA_RAT B2RZD6_RAT

36147.53

9.54

1

0.028

1.12515

0.789571

1.1596

0.469314

1.06957

0.929612

1.19075

0.495744

2

2

7.5

42031.18

6.85

0

0.204

0.858416

0.591837

1.0253

0.910903

0.996399

0.898191

1.00595

0.988791

20

9

26.5

39283.32

6.67

0

0.204

0.974703

0.879332

0.902992

0.60498

1.13142

0.795513

0.965984

0.87159

123

13

51.2

22939.28

10.27

0

1.065

1.091

0.857416

0.931311

0.713331

1.25909

0.540716

1.05172

0.857721

19

14

5.1

416863.4

5.94

0

0.336

1.11747

0.804707

0.916593

0.656123

0.940333

0.76254

0.86267

0.532256

19

15

4.2

532245.4

6.06

0

0.343

1.11747

0.804707

1.04077

0.855312

0.913604

0.700094

0.847873

0.489649

55

26

32.5

82651.56

6.55

0

0.22

1.06046

0.919012

1.17193

0.435537

1.18084

0.692385

1.31009

0.266138

5

2

16.5

25904.26

5.3

4

0.663

0.957099

0.833666

1.237

0.281882

1.14832

0.759732

1.39694

0.154002

26

13

13.2

8.02

12

0.274

1.04653

0.947273

1.02343

0.917663

1.24229

0.571848

1.20476

0.464318

1

1

1.4

92735.01

6.49

0

0.942

0.758319

0.38593

1.09764

0.658958

1.01767

0.950687

1.06665

0.815613

6

4

15.2

41945.85

4.89

0

0.33

1.08448

0.870498

0.765485

0.213155

1.30691

0.457005

0.786701

0.334563

1

1

2.3

32846.51

5.08

0

0.151

0.948146

0.810644

1.13718

0.534283

1.24579

0.565297

1.16654

0.552654

113868.2

274060.6

5.41

0

0.748

1.08071

0.878091

0.937992

0.739866

1.05755

0.95602

0.957812

0.842845

138902

6.44

0

0.33

1.03193

0.976998

1.06615

0.765748

1.05103

0.97036

1.05563

0.846653

18630.59

10.35

0

1.001

1.07681

0.885956

0.951382

0.79396

1.17487

0.704589

1.00816

0.982423

17.3

43250.25

9.32

0

0.098

1.09269

0.854036

1.00186

0.995925

0.881037

0.626696

0.779474

0.318597

4

15.7

49700.56

7.69

0

0.172

0.973914

0.877276

1.32231

0.143012

1.26759

0.525293

1.4721

0.089719

1

1

2.0

63383.22

6.16

0

0.298

0.946984

0.807668

1.15501

0.482253

1.03838

0.998224

1.03929

0.893071

1

1

1.5

86495.61

5.79

0

0.341

1.25218

0.554374

1.07003

0.752306

0.712627

0.312667

0.803064

0.372582

19

7

24.9

27777.97

4.69

0

0.512

1.08917

0.861094

1.2445

0.266892

1.26203

0.535362

1.66904

0.016048

38

17

38.8

47313.74

9.13

0

0.23

1.15188

0.737529

1.22532

0.306347

1.23794

0.580036

1.76443

0.00592

69

19

29.5

47267.83

9.03

0

0.443

1.03482

0.971106

0.862894

0.465729

1.14516

0.766394

1.00756

0.984137

24

14

19.1

80464.36

5.58

0

0.468

1.02601

0.989056

0.881719

0.528809

1.03163

0.985252

0.853799

0.506491

1

1

2.7

45092.64

6.05

0

0.334

1.22327

0.604873

0.795541

0.277533

1.1803

0.693479

0.984095

0.935851

1

1

2.8

66960.65

8.36

7

0.056

1.12868

0.782639

0.503641

0.008523

0.895254

0.658338

0.506786

0.026473

7

7

5.8

157256.7

8.85

0

0.76

1.04629

0.947761

0.974679

0.890333

1.32887

0.42114

1.24424

0.381952

10

7

9.5

113934.3

6.76

0

0.255

0.999674

0.944767

1.14711

0.50497

1.16714

0.720505

1.13135

0.640674

2

2

4.3

56492.82

6.28

0

0.112

1.05236

0.935443

1.09874

0.655321

1.16359

0.727852

1.12289

0.662688

17

4

40.2

9326.67

9.52

1

0.406

1.09044

0.858546

0.902725

0.603995

1.26023

0.538643

1.26405

0.344249

76

44

24.0

1

1

1.0

3

2

10.6

9

7

4

No. of Pages 73

D4A8P9_RAT

29.2

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Q6AYP5_RAT

11

NSC 16186

ALDOC_RAT

32

22 April 2015

AMRP_RAT

Succinyl-CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial OS = Rattus norvegicus GN = Suclg1 PE = 2 SV = 2 Alpha-2-macroglobulin receptor-associated protein OS = Rattus norvegicus GN = Lrpap1 PE = 1 SV = 2 Fructose-bisphosphate aldolase C OS = Rattus norvegicus GN = Aldoc PE = 1 SV = 3 Myelin basic protein transcript variant N (Fragment) OS = Rattus norvegicus GN = Mbp PE = 2 SV = 1 Cytoplasmic dynein 1 heavy chain 1 (Fragment) OS = Rattus norvegicus GN = Dync1h1 PE = 2 SV = 1 Cytoplasmic dynein 1 heavy chain 1 OS = Rattus norvegicus GN = Dync1h1 PE = 1 SV = 1 Vesicle-fusing ATPase OS = Rattus norvegicus GN = Nsf PE = 1 SV = 1 CD81 antigen OS = Rattus norvegicus GN = Cd81 PE = 2 SV = 1 Nicotinamide nucleotide transhydrogenase OS = Rattus norvegicus GN = Nnt PE = 2 SV = 1 ATP-binding cassette sub-family F member 1 (Fragment) OS = Rattus norvegicus GN = Abcf1 PE = 2 SV = 1 Protein Cadm1 (Fragment) OS = Rattus norvegicus GN = Cadm1 PE = 2 SV = 1 Protein Pptc7 OS = Rattus norvegicus GN = Pptc7 PE = 4 SV = 1 Protein Sptbn1 OS = Rattus norvegicus GN = Sptbn1 PE = 4 SV = 1 Protein Bai3 (Fragment) OS = Rattus norvegicus GN = Bai3 PE = 2 SV = 1 Protein RGD1561815 OS = Rattus norvegicus GN = RGD1561815 PE = 4 SV = 1 Voltage-dependent calcium channel gamma-8 subunit (Fragment) OS = Rattus norvegicus GN = Cacng8 PE = 2 SV = 1 Acyl-coenzyme A thioesterase 2, mitochondrial OS = Rattus norvegicus GN = Acot2 PE = 1 SV = 1 Synaptotagmin III OS = Rattus norvegicus GN = Syt3 PE = 2 SV = 1 Exocyst complex component 3 OS = Rattus norvegicus GN = Exoc3 PE = 1 SV = 1 14-3-3 protein theta OS = Rattus norvegicus GN = Ywhaq PE = 1 SV = 1 Aspartate aminotransferase, mitochondrial OS = Rattus norvegicus GN = Got2 PE = 1 SV = 2 2’,3’-cyclic-nucleotide 3’-phosphodiesterase OS = Rattus norvegicus GN = Cnp PE = 1 SV = 2 Disks large homolog 4 OS = Rattus norvegicus GN = Dlg4 PE = 1 SV = 1 Alanyl-tRNA editing protein Aarsd1 OS = Rattus norvegicus GN = Aarsd1 PE = 2 SV = 1 Probable G-protein coupled receptor 37 OS = Rattus norvegicus GN = Gpr37 PE = 2 SV = 1 Protein LOC685244 OS = Rattus norvegicus GN = LOC685244 PE = 4 SV = 1 Uncharacterized protein OS = Rattus norvegicus PE = 3 SV = 1 D-3-phosphoglycerate dehydrogenase OS = Rattus norvegicus GN = Phgdh PE = 1 SV = 3 Ndufa4 protein OS = Rattus norvegicus GN = Ndufa4 PE = 4 SV = 1

36

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

SUCA_RAT

NDUA5_RAT G3V7T8_RAT RAB7A_RAT D3ZSA9_RAT LEG9_RAT B2RYC4_RAT GRIA3_RAT GPM6A_RAT D4A678_RAT D4A1B8_RAT Q56A26_RAT Q5XIH3_RAT F1M2C7_RAT SNPH_RAT MYH10_RAT C8YL70_RAT RS11_RAT EFHD2_RAT F1LS65_RAT

F1LY09_RAT D3ZAA9_RAT D3ZC15_RAT TMED7_RAT

TIM9B_RAT NAC1_RAT HS90B_RAT

12.2

12783.92

9.65

0

0.295

1.15931

0.723283

0.809875

0.312484

1.04331

0.987367

0.755498

0.269256

1

1

2.9

43287.49

7.23

0

0.415

1.00011

0.94591

0.856647

0.445757

1.02307

0.964039

0.874122

0.566475

82

16

38.3

62276.84

5.95

0

0.267

1.06229

0.915297

0.937927

0.739607

1.16565

0.723573

1.02964

0.920688

2

2

22.4

13411.62

6.84

0

0.349

1.11418

0.811212

1.25905

0.239371

1.12349

0.812471

1.37357

0.179861

4

4

6.1

8.99

0

0.79

1.12989

0.780265

0.674726

0.084487

1.6012

0.119591

0.974576

0.901999

4

3

16.4

6.4

0

0.377

1.06167

0.916545

0.986018

0.937923

2.08791

0.003724

1.98641

0.00038

1

1

1.5

5.73

0

0.151

0.859294

0.593844

0.929051

0.704431

0.700123

0.294413

0.624357

0.090571

1

1

3.4

39945.49

9.36

0

0.218

1.14751

0.745963

1.10928

0.621026

1.01516

0.944466

0.994586

0.973293

1

1

1.6

66872.25

6.6

6

0.098

1.11864

0.8024

0.798333

0.284123

1.16213

0.73087

0.903277

0.658044

9

6

8.5

8.38

3

0.219

1.09146

0.856492

1.03052

0.892077

1.09834

0.866745

1.06032

0.833413

18

5

13.5

5.55

0

0.561

1.00877

0.968706

0.914511

0.648181

1.25217

0.553431

1.22585

0.419144

2

2

1.0

4.94

0

0.769

1.13294

0.774292

1.53751

0.014493

0.775688

0.415814

1.15909

0.570788

105907.9 23503.51 133441.5

100371.5 29890.88 280071.2

1

1

4.3

21112.21

5.59

0

0.195

1.21621

0.617523

0.824635

0.351382

1.30857

0.454235

0.968565

0.880706

2

2

21.8

15672.53

4.98

1

0.376

1.19298

0.659895

1.49147

0.025409

1.1037

0.855117

1.5213

0.060862

19

5

13.2

50730.43

8.37

0

0.272

1.10596

0.827542

0.954899

0.808345

1.04711

0.979002

0.959914

0.85022

1

1

1.8

64141.23

7.86

0

0.671

1.06954

0.900621

1.02685

0.90533

1.35019

0.387969

1.23018

0.41021

8

4

7.3

50924.56

5.61

0

0.502

1.08301

0.873459

1.01087

0.963164

1.0281

0.976501

1.02851

0.923908

17

13

7.8

5.47

0

0.855

1.01173

0.976532

1.05932

0.789603

1.05541

0.960723

0.891174

0.619299

1

1

4.4

41796.58

8.8

0

0.499

1.02013

0.998667

0.76437

0.210995

1.00325

0.915069

0.748253

0.255437

1

1

11.4

18430.51

10.31

0

0.607

1.03085

0.979197

1.01182

0.959721

0.70545

0.3021

0.653951

0.11881

6

4

18.8

26758.86

5.01

0

0.668

1.14034

0.759873

0.808296

0.308497

1.18209

0.689824

0.981311

0.925934

2

2

2.1

7.7

0

0.675

1.10408

0.831273

0.923845

0.684085

0.97493

0.845665

0.814523

0.400739

2

2

7.2

47759.24

5.68

0

0.183

1.06855

0.902631

0.986162

0.938529

1.51943

0.183296

1.29103

0.296862

3

2

4.0

63354.32

5.79

0

0.35

0.988419

0.915202

0.975338

0.893087

0.754393

0.37893

0.817195

0.407485

2

2

1.6

7.01

0

0.36

1.05383

0.932457

1.00461

0.985914

0.850531

0.561128

0.896732

0.636969

1

1

4.4

25478.69

6.43

0

0.208

0.917471

0.733115

1.05874

0.791646

0.966353

0.824857

1.04239

0.88423

1

1

25.7

4024.58

9.74

0

0.997

0.905011

0.702339

0.703494

0.115721

0.815281

0.489761

0.521343

0.031242

2

1

16.0

11350.87

6.64

0

0.393

1.04071

0.95912

0.807565

0.306663

0.856148

0.572948

0.780948

0.321812

3

3

2.9

4.82

0

0.035

1.0729

0.893836

0.740421

0.168335

1.10749

0.846913

0.930621

0.748899

25

16

22.8

4.97

0

0.678

1.04493

0.950544

1.1144

0.604676

1.03415

0.991505

1.29626

0.2882

233612.8

146782.5

141358.3

104155.5 83280.25

37

(continued on next page)

No. of Pages 73

Q6AYB7_RAT

1

NSC 16186

DPYL2_RAT

1

22 April 2015

Q32PW9_RAT

60S ribosomal protein L30 OS = Rattus norvegicus GN = Rpl30 PE = 3 SV = 2 Psmc6 protein (Fragment) OS = Rattus norvegicus GN = Psmc6 PE = 2 SV = 1 Dihydropyrimidinase-related protein 2 OS = Rattus norvegicus GN = Dpysl2 PE = 1 SV = 1 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 OS = Rattus norvegicus GN = Ndufa5 PE = 1 SV = 3 Discs, large (Drosophila) homolog-associated protein 3, isoform CRA_b OS = Rattus norvegicus GN = Dlgap3 PE = 4 SV = 1 Ras-related protein Rab-7a OS = Rattus norvegicus GN = Rab7a PE = 1 SV = 2 Protein Nomo1 OS = Rattus norvegicus GN = Nomo1 PE = 4 SV = 1 Galectin-9 OS = Rattus norvegicus GN = Lgals9 PE = 2 SV = 2 Protein Syvn1 OS = Rattus norvegicus GN = Syvn1 PE = 2 SV = 1 Glutamate receptor 3 OS = Rattus norvegicus GN = Gria3 PE = 1 SV = 1 Isoform 2 of Neuronal membrane glycoprotein M6-a OS = Rattus norvegicus GN = Gpm6a Protein Spta1 OS = Rattus norvegicus GN = Spta1 PE = 2 SV = 1 Protein Dctn3 OS = Rattus norvegicus GN = Dctn3 PE = 4 SV = 1 Protein Opalin OS = Rattus norvegicus GN = Opalin PE = 2 SV = 1 NADH dehydrogenase (Ubiquinone) flavoprotein 1 OS = Rattus norvegicus GN = Ndufv1 PE = 2 SV = 1 Protein Ildr2 (Fragment) OS = Rattus norvegicus GN = Ildr2 PE = 2 SV = 1 Syntaphilin OS = Rattus norvegicus GN = Snph PE = 4 SV = 1 Myosin-10 OS = Rattus norvegicus GN = Myh10 PE = 2 SV = 1 DNA-directed polymerase delta interacting protein 2 OS = Rattus norvegicus GN = Poldip2 PE = 2 SV = 1 40S ribosomal protein S11 OS = Rattus norvegicus GN = Rps11 PE = 1 SV = 3 EF-hand domain-containing protein D2 OS = Rattus norvegicus GN = Efhd2 PE = 1 SV = 1 Signal-induced proliferation-associated 1-like protein 1 (Fragment) OS = Rattus norvegicus GN = Sipa1l1 PE = 2 SV = 1 Protein Actr3b (Fragment) OS = Rattus norvegicus GN = Actr3b PE = 2 SV = 1 Protein Mpp2 OS = Rattus norvegicus GN = Mpp2 PE = 2 SV = 1 Protein Rltpr OS = Rattus norvegicus GN = Ube2j2 PE = 2 SV = 1 Transmembrane emp24 domain-containing protein 7 OS = Rattus norvegicus GN = Tmed7 PE = 1 SV = 1 Protein Ube2j2 OS = Rattus norvegicus GN = Ube2j2 PE = 2 SV = 1 Mitochondrial import inner membrane translocase subunit Tim9 B OS = Rattus norvegicus GN = Fxc1 PE = 3 SV = 1 Isoform 3 of Sodium/calcium exchanger 1 OS = Rattus norvegicus GN = Slc8a1 Heat shock protein HSP 90-beta OS = Rattus norvegicus GN = Hsp90ab1 PE = 1 SV = 4

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

RL30_RAT

B0K017_RAT

TPM1_RAT D3ZCV0_RAT D4AAM0_RAT Q5BJT9_RAT B4F7A3_RAT GPC1_RAT

MIC60_RAT Q5PQZ9_RAT ATPO_RAT D3ZT47_RAT Q6P2A7_RAT D3ZC55_RAT STML2_RAT D3ZJH9_RAT Q6DGG9_RAT CD166_RAT AIFM1_RAT AMD_RAT D4A5X1_RAT D4A8N2_RAT F1LQ05_RAT

Q5XIW9_RAT TBB4B_RAT D4ACB8_RAT

1.06519

0.909415

1.03478

0.876753

1.32986

0.419574

1.17469

0.533156

44537.97

8.02

0

0.083

1.05783

0.924345

1.15747

0.475293

0.931301

0.74124

1.07335

0.796901

9.6

16264.75

4.92

0

0.626

1.00213

0.951239

0.8432

0.404468

1.0461

0.981232

0.87892

0.581118

3.0

39374.75

4.85

0

0.115

0.89167

0.669918

0.906689

0.618707

1.08703

0.891381

1.08133

0.774748

28

12

30.0

4

2

2

1

16

11

41.6

4

4

5.8

1

1

1.3

70

16

40.0

1

1

5

100186.5

4.74

0

1.072

1.04847

0.943347

1.02397

0.915729

1.13766

0.782263

1.08918

0.753137

103832.5

5.31

0

0.605

0.979459

0.891746

1.05811

0.793841

1.17725

0.699713

0.981894

0.928009

104861.1

5.31

0

0.035

0.773037

0.413143

0.843158

0.404343

0.68783

0.277176

0.583992

0.061032

46961.18

8.58

0

0.411

1.03533

0.970075

0.985316

0.93497

1.02295

0.963736

0.996794

0.981183

5.2

18955.48

5.12

0

0.023

1.07764

0.884267

0.997022

0.984325

1.06174

0.946813

1.02079

0.94607

3

8.6

61733.53

6.86

0

0.365

1.01116

0.975016

0.765437

0.213063

1.1465

0.763576

0.915989

0.699754

2

2

1.1

5.66

19

0.043

0.93259

0.771044

0.781953

0.246952

1.21038

0.633212

0.896192

0.635244

40

22

25.1

82247.85

5.41

0

0.487

1.06113

0.917639

1.02388

0.916042

1.05883

0.953202

0.983054

0.932144

31

5

34.2

14358.69

9.41

1

0.472

1.05122

0.937742

1.02164

0.924159

1.03234

0.987024

0.98733

0.947386

28

9

39.0

23397.28

10.03

0

0.022

1.20314

0.64122

1.32029

0.145537

0.825988

0.510911

1.00425

0.993695

1

1

1.7

87275.77

8.41

0

0.355

1.01577

0.987164

1.07714

0.72783

0.756212

0.381998

0.785077

0.330931

6

6

19.4

47512.92

6.71

0

0.355

1.04285

0.95476

0.928896

0.703823

1.10918

0.843255

0.899516

0.645899

3

3

5.3

74829.44

6.18

0

0.23

0.9927

0.926435

0.792848

0.271276

1.1877

0.678446

0.821384

0.418195

4

4

16.9

33231.56

6.25

0

0.178

1.1003

0.83882

0.82435

0.350602

1.09102

0.882664

0.824585

0.426489

2

2

4.3

65350.91

7.87

0

0.148

1.20598

0.636037

1.47671

0.030166

1.0912

0.882284

1.20207

0.470262

1

1

4.1

32790.08

7.61

0

0.336

1.08521

0.869041

0.904762

0.611534

1.10131

0.860293

0.855726

0.512032

1

1

1.7

65021.21

5.77

1

0.37

1.0345

0.971764

0.86085

0.45914

1.30849

0.454374

1.02816

0.92492

9

7

10.0

66721.73

9.06

0

0.231

1.04034

0.959869

0.933221

0.720882

0.969105

0.831521

0.999326

0.990236

1

1

1.5

108673.9

5.78

1

0.355

1.87884

0.02843

0.90979

0.630319

1.06162

0.947071

1.09042

0.749723

1

1

2.5

89931.8

6.98

0

0.598

0.930966

0.766941

0.87454

0.504251

0.737469

0.351101

0.652546

0.117328

1

1

6.3

18770.01

5.62

0

0.272

0.914697

0.726225

0.897468

0.584734

0.93631

0.75303

0.792022

0.346643

7

6

20.4

38371.01

5.04

0

0.703

0.984573

0.905124

1.07451

0.736856

1.00503

0.91945

1.08696

0.759232

1

1

2.8

55561.67

6.59

0

0.201

1.0357

0.969316

0.994137

0.97215

0.838063

0.535322

0.950501

0.817304

4

4

12.5

38717.09

5.26

0

0.226

1.02554

0.990014

0.834746

0.379723

1.06358

0.942753

0.965901

0.871298

133

22

48.5

49800.45

4.79

0

0.357

1.00178

0.950306

1.07032

0.751308

1.29522

0.476774

1.52877

0.057241

13

7

12.4

59587.88

5.38

0

0.078

1.01653

0.989168

0.889331

0.555495

1.03451

0.992402

0.984615

0.937706

28343.11

221384.3

No. of Pages 73

D4AA31_RAT

0.083

2.4

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

SCN3A_RAT

Isoform 5 of Tropomyosin alpha-1 chain OS = Rattus norvegicus GN = Tpm1 Protein Actn2 OS = Rattus norvegicus GN = Actn2 PE = 4 SV = 1 Protein Tnpo3 OS = Rattus norvegicus GN = Tnpo3 PE = 2 SV = 1 Creatine kinase U-type, mitochondrial OS = Rattus norvegicus GN = Ckmt1b PE = 2 SV = 1 Hspc159 protein OS = Rattus norvegicus GN = Lgalsl PE = 2 SV = 1 Glypican-1 OS = Rattus norvegicus GN = Gpc1 PE = 1 SV = 1 Sodium channel protein type 3 subunit alpha OS = Rattus norvegicus GN = Scn3a PE = 1 SV = 1 Mitochondrial inner membrane protein OS = Rattus norvegicus GN = Immt PE = 2 SV = 1 NADH dehydrogenase [ubiquinone] 1 subunit C2 OS = Rattus norvegicus GN = Ndufc2 PE = 2 SV = 1 ATP synthase subunit O, mitochondrial OS = Rattus norvegicus GN = Atp5o PE = 1 SV = 1 Protein LOC100361389 OS = Rattus norvegicus GN = Fam171a2 PE = 4 SV = 1 Flot1 protein OS = Rattus norvegicus GN = Flot1 PE = 2 SV = 1 Heat shock 70kDa protein 12A (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Hspa12a PE = 4 SV = 1 Stomatin-like protein 2 OS = Rattus norvegicus GN = Stoml2 PE = 2 SV = 1 Malic enzyme OS = Rattus norvegicus GN = Me2 PE = 3 SV = 1 Calcium modulating ligand OS = Rattus norvegicus GN = Camlg PE = 2 SV = 1 CD166 antigen OS = Rattus norvegicus GN = Alcam PE = 1 SV = 1 Apoptosis-inducing factor 1, mitochondrial OS = Rattus norvegicus GN = Aifm1 PE = 1 SV = 1 Peptidyl-glycine alpha-amidating monooxygenase OS = Rattus norvegicus GN = Pam PE = 1 SV = 1 Protein Stim2 OS = Rattus norvegicus GN = Stim2 PE = 4 SV = 1 Protein Fdx1l OS = Rattus norvegicus GN = Fdx1l PE = 4 SV = 1 Endophilin-A1 (Fragment) OS = Rattus norvegicus GN = Sh3gl2 PE = 2 SV = 1 Protein Prcp OS = Rattus norvegicus GN = Prcp PE = 4 SV = 1 Flot2 protein OS = Rattus norvegicus GN = Flot2 PE = 2 SV = 1 Tubulin beta-4B chain OS = Rattus norvegicus GN = Tubb4b PE = 1 SV = 1 Chaperonin subunit 8 (Theta) (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Cct8 PE = 3 SV = 1

0

2

NSC 16186

CYB5B_RAT

5.08

2

22 April 2015

PGK1_RAT

26S proteasome non-ATPase regulatory subunit 2 OS = Rattus norvegicus GN = Psmd2 PE = 2 SV = 1 Phosphoglycerate kinase 1 OS = Rattus norvegicus GN = Pgk1 PE = 1 SV = 2 Cytochrome b5 type B OS = Rattus norvegicus GN = Cyb5b PE = 1 SV = 2 ADP-ribosylhydrolase like 2 OS = Rattus norvegicus GN = Adprhl2 PE = 2 SV = 1

38

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

PSMD2_RAT

ATP8_RAT PPIA_RAT ODPB_RAT

CD44_RAT NRX1A_RAT VISL1_RAT F8WG73_RAT QCR1_RAT ATP5H_RAT STX1B_RAT D4A8L9_RAT B5DFG5_RAT D3ZTR5_RAT TCPB_RAT NDKA_RAT SEPT2_RAT D3ZUB0_RAT NDUAA_RAT

G3V8D6_RAT Q5XIA6_RAT G3V8Q6_RAT

RPGF2_RAT SYNPR_RAT

G3V733_RAT KCRB_RAT

3.1

67885.74

8.39

0

0.153

1.05708

0.925851

1.32514

0.139522

0.587947

0.162405

0.668622

0.135162

3

3

6.8

60709.99

5.38

0

0.619

1.02812

0.98475

1.07955

0.719603

1.13091

0.796611

1.0439

0.879942

3

3

5.8

72187.52

8.88

0

0.066

1.24122

0.573271

0.979837

0.911942

0.900765

0.670773

0.996768

0.98109

6

1

14.9

7641.87

9.3

0

0.093

1.22423

0.60317

1.15008

0.496371

1.41512

0.297121

1.37523

0.177927

29

12

65.9

17874.13

8.34

0

0.326

1.01149

0.97588

1.2499

0.256441

1.26054

0.538075

1.82094

0.003115

35

13

38.2

38981.71

6.2

0

0.045

1.11225

0.815047

0.913021

0.64252

0.95877

0.806564

0.856159

0.513279

3

2

2.7

85731.49

4.83

0

0.784

1.03976

0.961048

0.993008

0.967384

1.14139

0.774363

0.81328

0.397625

4

4

3.8

166871.6

5.65

0

0.319

1.03201

0.976823

0.784254

0.251958

0.767387

0.40119

0.669517

0.136213

5

3

15.7

22142.1

5.01

0

0.502

1.16472

0.712945

0.869765

0.488253

1.40088

0.315717

2.57316

1.41E08

1 48

1 11

4.0 26.0

29713.26 52848.18

5.12 5.57

0 0

0.232 0.159

0.999688 1.00187

0.944802 0.950552

1.02125 1.20085

0.925561 0.362047

1.13902 0.968445

0.779369 0.829921

1.04051 1.04198

0.889606 0.885405

11

8

44.7

18763.21

6.16

0

0.702

1.13882

0.762836

1.90881

3.53E05

1.02835

0.977119

1.92459

0.000867

49

14

47.9

33244.34

5.25

1

0.694

0.993766

0.929234

0.965919

0.853821

1.15928

0.7368

1.09343

0.741519

1

1

3.6

55405.68

9.38

0

0.004

1.03219

0.97646

1.00384

0.988707

2.07582

0.004141

1.91504

0.000981

13

6

18.6

48594.81

6.14

0

0.657

1.13706

0.766262

1.01018

0.965701

1.28071

0.501942

1.11127

0.693393

2

1

3.3

84033.6

8.9

0

0.225

1.04803

0.944235

0.78973

0.264153

1.06927

0.93027

0.859407

0.522703

4

4

8.2

57457.69

6.01

0

0.021

0.999689

0.944806

1.06812

0.758912

0.713702

0.314272

0.657578

0.1227

11

3

25.7

17192.54

5.96

0

0.239

1.05818

0.923631

0.998551

0.99078

0.821873

0.502725

1.01717

0.956492

10

6

20.5

41592.07

6.15

1

0.539

1.02416

0.99281

1.08055

0.716223

0.883936

0.633096

0.998058

0.985703

1

1

4.9

38089.56

4.67

0

0.996

1.0418

0.956892

1.15173

0.491609

0.947891

0.780501

1.17357

0.535807

10

7

20.3

40492.6

7.64

0

0.436

0.96904

0.864591

0.982353

0.922508

1.03159

0.985149

1.16496

0.556474

4

3

4.4

80759.56

8.01

0

0.314

0.959657

0.840272

0.867829

0.481849

1.03019

0.981689

0.912607

0.688563

1

1

2.4

69760.01

7.08

1

0.189

1.25193

0.554797

1.19973

0.364743

0.663236

0.24479

0.869135

0.551446

11

7

24.7

45479.71

4.81

0

0.499

1.07809

0.883367

0.902208

0.602087

1.35

0.388256

1.07756

0.785195

4

4

5.1

6.12

0

0.657

1.02556

0.989968

0.750902

0.186132

1.16451

0.725942

1.15027

0.592603

2

1

5.3

29106.73

6.07

4

0.118

0.999279

0.943726

0.967742

0.861397

0.939488

0.76054

0.916017

0.699847

6

4

27.7

17608.89

9.81

0

0.812

0.913559

0.723403

1.05048

0.82074

0.902079

0.673752

1.01982

0.948858

25

9

18.8

63411.89

8.59

0

0.457

0.889872

0.665594

1.04333

0.846167

1.17609

0.70209

1.26822

0.336619

17

11

32.6

42724.79

5.39

0

0.466

0.937571

0.783664

0.951867

0.795938

1.00721

0.924824

0.919401

0.71111

164514.9

39

(continued on next page)

No. of Pages 73

F1LXA0_RAT

1

NSC 16186

G3V7V3_RAT

1

22 April 2015

PAK3_RAT

Acyl-CoA synthetase family member 2, mitochondrial OS = Rattus norvegicus GN = Acsf2 PE = 2 SV = 1 Serine/threonine-protein kinase PAK 3 OS = Rattus norvegicus GN = Pak3 PE = 1 SV = 1 Protein Slc27a4 OS = Rattus norvegicus GN = Slc27a4 PE = 4 SV = 1 ATP synthase protein 8 OS = Rattus norvegicus GN = Mtatp8 PE = 1 SV = 1 Peptidyl-prolyl cis-trans isomerase A OS = Rattus norvegicus GN = Ppia PE = 1 SV = 2 Pyruvate dehydrogenase E1 component subunit beta, mitochondrial OS = Rattus norvegicus GN = Pdhb PE = 1 SV = 2 CD44 antigen OS = Rattus norvegicus GN = Cd44 PE = 2 SV = 1 Isoform 10a of Neurexin-1 OS = Rattus norvegicus GN = Nrxn1 Visinin-like protein 1 OS = Rattus norvegicus GN = Vsnl1 PE = 1 SV = 2 Basigin OS = Rattus norvegicus GN = Bsg PE = 4 SV = 1 Cytochrome b-c1 complex subunit 1, mitochondrial OS = Rattus norvegicus GN = Uqcrc1 PE = 1 SV = 1 ATP synthase subunit d, mitochondrial OS = Rattus norvegicus GN = Atp5h PE = 1 SV = 3 Syntaxin-1B OS = Rattus norvegicus GN = Stx1b PE = 1 SV = 1 Protein Btbd17 OS = Rattus norvegicus GN = Btbd17 PE = 4 SV = 1 Protein Sept6 (Fragment) OS = Rattus norvegicus GN = Sept6 PE = 2 SV = 1 Protein Scand3 OS = Rattus norvegicus GN = Zbed5 PE = 4 SV = 1 T-complex protein 1 subunit beta OS = Rattus norvegicus GN = Cct2 PE = 1 SV = 3 Nucleoside diphosphate kinase A OS = Rattus norvegicus GN = Nme1 PE = 1 SV = 1 Septin-2 OS = Rattus norvegicus GN = Sept2 PE = 1 SV = 1 Protein Rcn1 OS = Rattus norvegicus GN = Rcn1 PE = 4 SV = 1 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial OS = Rattus norvegicus GN = Ndufa10 PE = 1 SV = 1 Tripartite motif protein 3, isoform CRA_a OS = Rattus norvegicus GN = Trim3 PE = 4 SV = 1 Protein Smpd1 OS = Rattus norvegicus GN = Smpd1 PE = 2 SV = 1 Protein kinase, cAMP-dependent, regulatory, type 2, alpha, isoform CRA_a OS = Rattus norvegicus GN = Prkar2a PE = 4 SV = 1 Rap guanine nucleotide exchange factor 2 OS = Rattus norvegicus GN = Rapgef2 PE = 4 SV = 1 Synaptoporin OS = Rattus norvegicus GN = Synpr PE = 2 SV = 2 Protein Ndufa12 (Fragment) OS = Rattus norvegicus GN = Ndufa12 PE = 4 SV = 1 Synapsin II, isoform CRA_a OS = Rattus norvegicus GN = Syn2 PE = 4 SV = 1 Creatine kinase B-type OS = Rattus norvegicus GN = Ckb PE = 1 SV = 2

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

ACSF2_RAT

LANC1_RAT IMPA1_RAT ACSL6_RAT CTBP1_RAT B4F7C2_RAT MACD1_RAT D4A133_RAT

D3ZTW9_RAT D3ZH41_RAT I1T7F1_RAT TCPD_RAT TBB5_RAT F8WFM2_RAT MP2K1_RAT D3Z9H2_RAT F1LR80_RAT D3ZRF5_RAT Q1RP74_RAT C1TC_RAT Q9QXG3_RAT F1LYS1_RAT HSP7C_RAT TBB2A_RAT

GLPK_RAT D4A5J2_RAT

0.927456

0.758098

1.04182

0.851555

1.12181

0.816052

1.19409

0.488161

6.73

0

0.564

1.02132

0.998607

0.891053

0.561622

0.875954

0.615544

0.761207

0.280499

43656.28

6.41

0

0.482

1.03563

0.969457

0.885942

0.543535

1.08652

0.892481

0.991038

0.960619

11.0

45239.44

7.57

0

0.177

0.971858

0.871922

1.08616

0.697198

1.04295

0.988176

0.847051

0.487336

4

14.4

30511.01

5.17

0

0.023

1.03631

0.968074

0.913675

0.645002

0.986515

0.873939

0.809399

0.387995

10

5

8.2

80947.69

6.57

0

0.161

0.987444

0.912644

0.921601

0.675381

1.21911

0.616148

1.21591

0.440115

2

2

7.3

47758.02

6.28

0

0.117

0.990405

0.920411

0.938144

0.740474

1.08515

0.895476

0.983072

0.932205

105

19

48.7

49585.25

4.78

0

0.321

1.01193

0.977055

1.30015

0.172646

1.21566

0.622858

1.54997

0.04793

1

1

5.4

28642.72

8.69

0

0.26

0.995725

0.934383

1.21455

0.330117

0.98163

0.861995

1.57478

0.038681

20

10

21.1

68264.26

5.42

0

0.19

0.981099

0.896033

1.0757

0.732758

0.937324

0.755422

1.07561

0.790596

8

5

16.5

46209.76

7.7

0

0.011

0.955899

0.830571

1.12031

0.586002

0.845594

0.550838

1.01671

0.957809

6

3

11.1

41326.34

8.86

0

0.443

0.799634

0.465107

1.0694

0.754484

0.95232

0.791084

0.874991

0.569113

2

2

4.7

63546.33

5.44

0

0.503

0.837989

0.546048

1.06612

0.765832

1.28537

0.493789

1.19451

0.487214

57

9

23.6

54500.7

5.86

0

0.411

0.966186

0.857179

0.78686

0.257711

1.26457

0.530756

1.04385

0.88007

5

4

10.8

58098.8

8.24

0

0.003

1.04609

0.948174

0.86335

0.467205

1.16806

0.718595

1.04205

0.885218

123

22

48.7

49670.28

4.78

0

0.348

1.00761

0.965671

1.25104

0.254262

1.15474

0.746271

1.44923

0.106462

15

9

29.5

33556.58

5.32

0

0.456

0.956897

0.833144

1.0642

0.772537

1.06938

0.930028

1.28989

0.298758

3

1

3.6

43464.54

6.18

0

0.3

1.56637

0.163482

1.29622

0.178359

0.977356

0.851569

1.58754

0.034549

8

5

15.8

42728.94

9.12

0

0.2

0.903164

0.697815

1.03204

0.886609

0.918461

0.711305

0.751932

0.26239

7

6

13.5

54120.95

5.37

0

0.436

1.00223

0.951492

0.793858

0.273611

0.789391

0.44063

0.72055

0.207174

29

10

34.1

34661.99

9.26

2

0.179

1.05736

0.925296

1.29793

0.175852

1.28026

0.50274

1.71517

0.010043

2

1

4.1

27247.09

4.93

0

0.537

1.24704

0.563208

1.04011

0.857671

1.14688

0.762778

1.03492

0.905574

1

1

0.8

100994.3

7.05

0

0.063

0.986652

0.910568

0.90272

0.603978

1.19819

0.657376

0.982111

0.928785

12

6

22.6

33152.3

5.2

1

0.608

0.905248

0.70292

0.928506

0.702292

1.13649

0.784727

1.05069

0.860647

4

3

2.7

158257.5

9.65

0

0.936

0.977351

0.88624

0.90182

0.600659

1.12549

0.808179

1.12418

0.659301

62

21

36.8

70870.22

5.37

0

0.452

1.01779

0.992509

1.04812

0.829108

1.09402

0.876129

1.09901

0.726328

137

21

48.3

49906.45

4.78

0

0.408

1.00313

0.95387

1.25104

0.25427

1.15822

0.739016

1.36007

0.196206

1

1

7.1

26379.2

6.33

0

0.319

0.713824

0.31054

0.964834

0.849323

0.628931

0.204196

0.525115

0.032592

7

5

9.8

61231.83

5.64

0

0.035

1.01868

0.994839

1.14467

0.512083

1.08798

0.889312

0.980548

0.92322

1

1

7.2

23433.9

8.94

0

0.167

0.892511

0.671944

1.2722

0.21629

0.716619

0.31865

0.69563

0.169741

4

4

5.6

1

1

2.8

4

3

4

72794.57 111908.1

No. of Pages 73

KAD2_RAT

0.363

3.6

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

S2546_RAT

0

3

NSC 16186

Q6AYD3_RAT

5.09

4

22 April 2015

ARHG2_RAT

Protein Tbc1d17 OS = Rattus norvegicus GN = Tbc1d17 PE = 2 SV = 1 Rho guanine nucleotide exchange factor 2 OS = Rattus norvegicus GN = Arhgef2 PE = 2 SV = 1 Proliferation-associated 2G4 OS = Rattus norvegicus GN = Pa2g4 PE = 2 SV = 1 LanC-like protein 1 OS = Rattus norvegicus GN = Lancl1 PE = 2 SV = 2 Inositol monophosphatase 1 OS = Rattus norvegicus GN = Impa1 PE = 1 SV = 2 Isoform 2 of Long-chain-fatty-acid–CoA ligase 6 OS = Rattus norvegicus GN = Acsl6 C-terminal-binding protein 1 OS = Rattus norvegicus GN = Ctbp1 PE = 2 SV = 1 RCG45085 OS = Rattus norvegicus GN = Tubb4 PE = 2 SV = 1 O-acetyl-ADP-ribose deacetylase MACROD1 (Fragment) OS = Rattus norvegicus GN = Macrod1 PE = 2 SV = 2 Protein Atp6v1a OS = Rattus norvegicus GN = Atp6v1a PE = 3 SV = 1 Solute carrier family 25 member 46 OS = Rattus norvegicus GN = Slc25a46 PE = 2 SV = 2 Endonuclease G-like 1 (Predicted), isoform CRA_d OS = Rattus norvegicus GN = Exog PE = 4 SV = 1 Protein Ckap4 OS = Rattus norvegicus GN = Ckap4 PE = 4 SV = 1 Amino acid transporter OS = Rattus norvegicus PE = 2 SV = 1 T-complex protein 1 subunit delta OS = Rattus norvegicus GN = Cct4 PE = 1 SV = 3 Tubulin beta-5 chain OS = Rattus norvegicus GN = Tubb5 PE = 1 SV = 1 Beta-soluble NSF attachment protein OS = Rattus norvegicus GN = Napb PE = 4 SV = 1 Dual specificity mitogen-activated protein kinase kinase 1 OS = Rattus norvegicus GN = Map2k1 PE = 1 SV = 2 Hyaluronan and proteoglycan link protein 4 (Predicted) OS = Rattus norvegicus GN = Hapln4 PE = 4 SV = 1 CaM kinase-like vesicle-associated protein OS = Rattus norvegicus GN = Camkv PE = 2 SV = 1 Protein Slc25a22 OS = Rattus norvegicus GN = Slc25a22 PE = 3 SV = 1 Protein Tbcb OS = Rattus norvegicus GN = Tbcb PE = 2 SV = 1 C-1-tetrahydrofolate synthase, cytoplasmic OS = Rattus norvegicus GN = Mthfd1 PE = 1 SV = 3 Syntaxin 1A OS = Rattus norvegicus GN = Stx1a PE = 2 SV = 1 Uncharacterized protein (Fragment) OS = Rattus norvegicus PE = 2 SV = 1 Heat shock cognate 71 kDa protein OS = Rattus norvegicus GN = Hspa8 PE = 1 SV = 1 Tubulin beta-2A chain OS = Rattus norvegicus GN = Tubb2a PE = 1 SV = 1 Adenylate kinase 2, mitochondrial OS = Rattus norvegicus GN = Ak2 PE = 2 SV = 2 Glycerol kinase OS = Rattus norvegicus GN = Gk PE = 2 SV = 1 5’,3’-nucleotidase, mitochondrial (Predicted) OS = Rattus norvegicus GN = Nt5m PE = 4 SV = 1

40

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

B1H264_RAT

B5DFK6_RAT D4A9Q5_RAT 68MP_RAT ATLA1_RAT D3ZLD5_RAT F1LYK8_RAT D3ZXK9_RAT HOME1_RAT IDH3B_RAT H1UBM8_RAT ADDG_RAT G3V9D3_RAT TBB3_RAT PEBP1_RAT CISD1_RAT D3ZVQ8_RAT F1M9N9_RAT THTR_RAT F1LZ38_RAT D4A7D8_RAT D3ZBS6_RAT ETFB_RAT TBB2B_RAT D4AB81_RAT

O89035_RAT TRAP1_RAT EIF3A_RAT

0.281

0.960351

0.842065

0.936138

0.732469

1.05468

0.962334

0.997372

0.983251

6.52

0

0.48

0.975083

0.880324

0.871684

0.494649

1.124

0.811364

0.960197

0.851215

7.48

0

0.165

0.951057

0.818114

0.848338

0.419968

1.00229

0.912684

0.888603

0.611198

6.73

0

0.48

0.873125

0.625862

1.1311

0.552652

1.04784

0.977386

1.08708

0.758897

50319.91

8.05

0

0.298

0.778292

0.423129

0.99265

0.965875

0.673339

0.257757

0.626231

0.092183

11.7

6914.16

9.93

0

0.135

1.13463

0.770989

1.06027

0.786252

1.27945

0.504167

1.41278

0.138146

2 1

3.8 0.8

63374.57 162543

5.76 5.27

2 0

0.294 0.809

0.871114 0.599759

0.621161 0.164194

0.937418 1.05513

0.737574 0.804339

0.917903 2.05652

0.710013 0.004894

0.838788 1.61242

0.464429 0.027565

1

1

1.6

127026

5.88

0

0.426

0.701445

0.291422

0.538523

0.014445

0.665262

0.247352

0.423059

0.009477

1

1

8.8

24336.33

6.65

0

0.215

1.09727

0.844859

1.05806

0.794008

1.07407

0.91974

1.09311

0.742369

2

2

7.7

41304.34

5.39

0

-0.807

0.850601

0.574113

0.847495

0.4174

0.989853

0.882116

0.794859

0.353194

36

15

33.5

42353.41

8.89

0

0.133

1.02214

0.996938

1.24381

0.26823

0.959961

0.809428

1.27002

0.333367

1

1

2.2

62407.45

5.92

0

0.294

0.98799

0.914077

1.16333

0.458954

0.842149

0.543713

0.86391

0.535911

2.6

6

4

4.1

14

10

11.8

2

2

1.5

1

1

3.6

1

1

2 1

46768.12 133551.5 98785.84 135665.3

2

2

4.8

75360.54

5.75

0

0.543

1.01871

0.994928

0.702522

0.114534

0.704591

0.300852

0.51055

0.027642

1

1

1.0

88522.44

5.32

0

0.409

1.19212

0.661496

0.792676

0.270878

1.30266

0.464144

0.871875

0.559678

91

18

39.1

50418.13

4.82

0

0.371

0.989093

0.91697

1.25815

0.241011

1.15947

0.736399

1.59416

0.032556

7

4

20.9

20801.14

5.47

0

0.569

1.03766

0.965321

1.31668

0.150139

0.76084

0.389878

1.09818

0.728592

24

7

52.8

12096.82

8.99

1

0.378

0.967143

0.859662

0.894437

0.57376

0.969746

0.833074

0.97816

0.914727

5

3

9.9

27155.94

5.99

0

0.23

0.957776

0.835413

1.08784

0.691556

1.00427

0.917569

1.22342

0.424219

65

41

13.9

5.04

0

0.662

0.989326

0.917579

0.942837

0.759307

0.985342

0.871067

0.918741

0.708907

4

3

15.5

7.71

0

0.439

0.989126

0.917055

1.14635

0.507187

0.766306

0.399308

1.0225

0.941176

2

2

1.2

314168.7

6.04

0

0.403

1.13275

0.774663

1.00409

0.987808

1.28998

0.485786

0.880761

0.586783

1

1

0.5

391732.8

6.34

0

0.189

1.07299

0.893658

0.723103

0.141773

1.56643

0.144155

1.12829

0.648608

4

3

8.0

45094.09

5.54

0

0.596

0.987942

0.913951

1.01355

0.953444

0.72235

0.327367

0.837321

0.460424

11

5

25.1

27687.1

7.61

0

0.076

1.0274

0.986226

1.13837

0.530723

0.790787

0.443205

0.974136

0.900436

118

21

48.3

49952.54

4.78

0

0.406

0.986484

0.910128

1.28026

0.202963

1.2238

0.607066

1.46741

0.09297

2

2

1.3

6.15

0

0.304

1.11554

0.808533

1.03408

0.879301

1.0832

0.899736

1.08104

0.775557

3

1

2.9

51043.51

8.61

0

0.139

1.07003

0.899625

1.11956

0.58835

0.852099

0.564416

0.90177

0.653167

3

2

9.1

31454.33

9.42

0

0.091

0.816913

0.500722

1.29112

0.185969

1.04469

0.984342

1.00165

0.998538

6

3

5.8

80460.21

6.56

0

0.355

0.992872

0.926887

1.11405

0.605781

0.761612

0.391201

0.935174

0.764413

1

1

0.6

6.38

0

1.464

0.998218

0.940937

0.982182

0.921789

0.910267

0.692427

0.848073

0.490213

426282.8 33406.34

184570.7

163193.9

41

(continued on next page)

No. of Pages 73

KAT3_RAT

0

1

NSC 16186

GRIA2_RAT

8.5

1

22 April 2015

G3V8G5_RAT

Protein Agk OS = Rattus norvegicus GN = Agk PE = 4 SV = 1 Golgi apparatus protein 1 OS = Rattus norvegicus GN = Glg1 PE = 4 SV = 1 Glutamate receptor 2 OS = Rattus norvegicus GN = Gria2 PE = 4 SV = 1 Adaptor-related protein complex 3, delta 1 subunit, isoform CRA_b OS = Rattus norvegicus GN = Ap3d1 PE = 2 SV = 1 Carboxypeptidase M (Predicted) OS = Rattus norvegicus GN = Cpm PE = 4 SV = 1 6.8 kDa mitochondrial proteolipid OS = Rattus norvegicus GN = Mp68 PE = 1 SV = 1 Atlastin-1 OS = Rattus norvegicus GN = Atl1 PE = 1 SV = 1 Protein Golga3 OS = Rattus norvegicus GN = Golga3 PE = 4 SV = 1 Protein Cadps2 (Fragment) OS = Rattus norvegicus GN = Cadps2 PE = 2 SV = 1 Nucleoside phosphorylase (Mapped), isoform CRA_b OS = Rattus norvegicus GN = Pnp PE = 4 SV = 1 Homer protein homolog 1 OS = Rattus norvegicus GN = Homer1 PE = 1 SV = 2 Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial OS = Rattus norvegicus GN = Idh3B PE = 1 SV = 1 Copine 4 protein OS = Rattus norvegicus GN = Cpne4 PE = 2 SV = 1 Isoform 1 of Gamma-adducin OS = Rattus norvegicus GN = Add3 Protein sel-1 homolog 1 OS = Rattus norvegicus GN = Sel1l PE = 4 SV = 1 Tubulin beta-3 chain OS = Rattus norvegicus GN = Tubb3 PE = 1 SV = 1 Phosphatidylethanolamine-binding protein 1 OS = Rattus norvegicus GN = Pebp1 PE = 1 SV = 3 CDGSH iron-sulfur domain-containing protein 1 OS = Rattus norvegicus GN = Cisd1 PE = 3 SV = 1 Protein Gstm6 OS = Rattus norvegicus GN = Gstm6 PE = 3 SV = 1 Protein Ank2 (Fragment) OS = Rattus norvegicus GN = Ank2 PE = 2 SV = 1 Thiosulfate sulfurtransferase OS = Rattus norvegicus GN = Tst PE = 1 SV = 3 Protein Tenm4 OS = Rattus norvegicus GN = Tenm4 PE = 2 SV = 1 Protein Wdfy3 OS = Rattus norvegicus GN = Wdfy3 PE = 2 SV = 1 Protein RGD1559864 OS = Rattus norvegicus GN = RGD1559864 PE = 2 SV = 1 Electron transfer flavoprotein subunit beta OS = Rattus norvegicus GN = Etfb PE = 2 SV = 3 Tubulin beta-2B chain OS = Rattus norvegicus GN = Tubb2b PE = 1 SV = 1 Uncharacterized protein OS = Rattus norvegicus PE = 2 SV = 1 Kynurenine–oxoglutarate transaminase 3 OS = Rattus norvegicus GN = Ccbl2 PE = 2 SV = 1 Mitochondrial dicarboxylate carrier OS = Rattus norvegicus GN = Slc25a10 PE = 2 SV = 1 Heat shock protein 75 kDa, mitochondrial OS = Rattus norvegicus GN = Trap1 PE = 1 SV = 1 Eukaryotic translation initiation factor 3 subunit A OS = Rattus norvegicus GN = Eif3a PE = 2 SV = 2

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

D3Z9L0_RAT

SPG7_RAT RASK_RAT F1LP30_RAT G3V8G4_RAT G3V6Y6_RAT ACSL1_RAT B2GV15_RAT

THEM4_RAT SCN3B_RAT Q6DUV1_RAT SIR5_RAT G3V8V3_RAT D3ZYH3_RAT RPN2_RAT

AP2A2_RAT MMSA_RAT

LONM_RAT Q6AZ44_RAT NSMA_RAT RAC1_RAT G3V936_RAT LGUL_RAT

SEP11_RAT D3ZJ86_RAT

58205.83

8.84

0

0.374

0.917614

0.733474

0.921966

0.676796

1.0146

0.94308

0.919186

0.710393

14

8

23.1

34658.83

5.32

0

0.549

0.959656

0.840268

1.10897

0.622034

1.1849

0.684119

1.36459

0.190611

4

3

8.1

54983.68

8.23

0

0.381

0.953642

0.82476

0.975981

0.89578

0.91505

0.703423

0.87762

0.577132

5

5

8.7

82121.87

9.15

2

0.198

0.963852

0.851126

1.08494

0.701334

1.23968

0.576762

1.29668

0.287518

5

5

30.2

21655.59

6.33

0

0.433

0.836541

0.542871

0.562235

0.020312

1.03047

0.982389

0.98128

0.925824

2

2

4.2

79294.77

6.66

0

0.287

0.796585

0.458971

0.895776

0.578594

1.02022

0.95699

0.86952

0.552599

9

4

6.1

96000.21

4.86

0

0.421

0.977613

0.886925

0.602959

0.03529

1.31998

0.435454

0.879463

0.582785

17

11

16.5

96736.83

6.31

0

0.332

0.993787

0.92929

1.06292

0.777

1.03758

1

1.07495

0.792446

4

4

8.4

78177.8

6.6

1

0.08

1.12706

0.785829

1.1375

0.533348

0.774101

0.412994

0.91278

0.689132

1

1

2.7

53272.86

8.57

0

0.157

0.985951

0.908733

0.9218

0.676152

1.05512

0.96137

0.697228

0.171979

11

7

13.7

50442.94

8.8

0

0.28

0.984001

0.903624

0.902729

0.604009

1.09215

0.880206

1.05952

0.835654

2

1

7.8

26089.02

9.11

0

0.282

0.986063

0.909026

1.106

0.63163

0.641633

0.218615

0.84059

0.469372

1

1

4.9

30307.24

4.98

0

0.19

0.906416

0.705784

1.07151

0.747172

1.07586

0.915805

1.05304

0.853968

4

4

7.1

83574.68

6.62

0

0.44

0.908984

0.712103

0.800078

0.288296

0.71815

0.320964

0.889583

0.614278

5

4

10.3

34097.94

9.08

0

0.266

1.06446

0.910903

0.998535

0.990713

1.1575

0.740512

1.1133

0.687989

13

8

11.4

97287.19

6.65

0

0.394

0.967087

0.859516

1.16847

0.444871

1.28588

0.492897

1.4244

0.127343

1

1

8.5

18592.78

5.54

0

0.754

0.936725

0.781516

0.928034

0.70044

0.760167

0.388726

0.75958

0.277263

1

1

3.7

69122.12

5.57

0

0.092

1.0402

0.96015

0.941257

0.752948

0.93208

0.74307

1.08853

0.754921

10

7

10.1

6.51

0

0.093

1.06616

0.907462

1.42584

0.052842

0.793022

0.447345

1.04344

0.881254

4

4

8.0

8.47

1

0.048

1.07042

0.898849

1.24783

0.260404

1.00734

0.925152

1.1414

0.614954

4

3

4.6

6.17

0

0.287

0.915612

0.728496

1.06015

0.786679

1.13044

0.797598

1.26616

0.340376

1

1

2.8

35988.77

7.26

0

0.262

1.04008

0.960397

1.26306

0.232163

1.02065

0.958058

1.3779

0.174846

1

1

2.6

47644.17

6.61

2

0.135

0.920388

0.740388

0.820388

0.339888

0.964115

0.819447

0.861888

0.529959

14

6

33.3

21449.86

8.77

0

0.101

0.916707

0.731217

0.76876

0.219597

1.18533

0.683249

1.04968

0.863488

41

9

15.2

51830.11

8.58

0

0.176

0.919336

0.737762

1.00534

0.983269

1.13901

0.779392

1.12044

0.669116

5

2

9.8

20819.37

5.12

0

0.552

1.0544

0.93129

1.27463

0.212211

0.896291

0.660671

1.12009

0.670022

29 2

17 2

22.4 7.9

96268.73 38731.22

6.44 5.67

0 0

0.526 0.251

0.962608 0.975116

0.847904 0.88041

1.09581 0.642816

0.665003 0.058212

0.969923 1.1105

0.833505 0.840393

1.09285 0.715879

0.743091 0.199736

12

6

16.9

49694.07

6.24

0

0.697

1.08367

0.87213

0.959178

0.825936

1.15592

0.74382

1.11021

0.696211

3

2

2.7

78011.09

5.92

0

0.273

0.896372

0.681278

1.04776

0.830397

1.05216

0.967891

1.20587

0.461881

104043.3 57806.97

105791.3

No. of Pages 73

DYN1_RAT GBB5_RAT

3.7

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Q5U2X8_RAT

1

NSC 16186

F1LMV9_RAT

2

22 April 2015

D3ZU08_RAT

Ubiquitin carboxyl-terminal hydrolase OS = Rattus norvegicus GN = Usp30 PE = 3 SV = 1 Protein Napg OS = Rattus norvegicus GN = Napg PE = 4 SV = 1 Coronin (Fragment) OS = Rattus norvegicus GN = Coro2b PE = 2 SV = 1 Paraplegin OS = Rattus norvegicus GN = Spg7 PE = 2 SV = 1 GTPase KRas OS = Rattus norvegicus GN = Kras PE = 1 SV = 3 Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial OS = Rattus norvegicus GN = Mccc1 PE = 2 SV = 1 Brevican core protein OS = Rattus norvegicus GN = Bcan PE = 4 SV = 1 Phosphorylase OS = Rattus norvegicus GN = Pygb PE = 3 SV = 1 Long-chain-fatty-acid–CoA ligase 1 OS = Rattus norvegicus GN = Acsl1 PE = 1 SV = 1 Dihydrolipoamide branched chain transacylase E2 OS = Rattus norvegicus GN = Dbt PE = 2 SV = 1 Acyl-CoA thioesterase 9 OS = Rattus norvegicus GN = Acot9 PE = 2 SV = 1 Acyl-coenzyme A thioesterase THEM4 OS = Rattus norvegicus GN = Them4 PE = 2 SV = 1 Sodium channel subunit beta-3 OS = Rattus norvegicus GN = Scn3b PE = 2 SV = 1 Protein kinase C epsilon OS = Rattus norvegicus GN = Prkce PE = 2 SV = 1 NAD-dependent protein deacylase sirtuin-5, mitochondrial OS = Rattus norvegicus GN = Sirt5 PE = 2 SV = 1 Phosphorylase OS = Rattus norvegicus GN = Pygm PE = 3 SV = 1 Protein Nudt10 OS = Rattus norvegicus GN = Nudt10 PE = 3 SV = 1 Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit 2 (Fragment) OS = Rattus norvegicus GN = Rpn2 PE = 4 SV = 1 AP-2 complex subunit alpha-2 OS = Rattus norvegicus GN = Ap2a2 PE = 1 SV = 3 Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial OS = Rattus norvegicus GN = Aldh6a1 PE = 1 SV = 1 Lon protease homolog, mitochondrial OS = Rattus norvegicus GN = Lonp1 PE = 2 SV = 1 Acyl-CoA thioesterase 8 OS = Rattus norvegicus GN = Acot8 PE = 2 SV = 1 Sphingomyelin phosphodiesterase 2 OS = Rattus norvegicus GN = Smpd2 PE = 1 SV = 1 Ras-related C3 botulinum toxin substrate 1 OS = Rattus norvegicus GN = Rac1 PE = 1 SV = 1 Citrate synthase OS = Rattus norvegicus GN = Cs PE = 3 SV = 1 Lactoylglutathione lyase OS = Rattus norvegicus GN = Glo1 PE = 1 SV = 3 Isoform 4 of Dynamin-1 OS = Rattus norvegicus GN = Dnm1 Guanine nucleotide-binding protein subunit beta-5 OS = Rattus norvegicus GN = Gnb5 PE = 2 SV = 1 Septin-11 OS = Rattus norvegicus GN = Sept11 PE = 1 SV = 1 Sodium/hydrogen exchanger OS = Rattus norvegicus GN = Slc9a6 PE = 2 SV = 1

42

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

D3ZPG5_RAT

B2B9B0_RAT RL27_RAT DC1L1_RAT REEP5_RAT FAAA_RAT DGKB_RAT D4A3Z3_RAT D3ZDX7_RAT F1LUW9_RAT USO1_RAT K6PL_RAT Q5RKJ9_RAT NEUL_RAT CPPED_RAT HS105_RAT B2RYG2_RAT F1LMR7_RAT CBPE_RAT G3V9Z3_RAT PGRC1_RAT PP2BA_RAT D4ACU6_RAT RALB_RAT DPYL1_RAT

Q3B7V5_RAT STXB1_RAT

0.406

0.933526

0.773411

1.03628

0.871401

1.35816

0.375979

1.03175

0.914625

136893

5.45

0

0.188

0.936416

0.780733

0.948844

0.783621

1.13017

0.798182

1.1284

0.648315

1.8

109274.6

8.54

3

0.13

0.958498

0.837277

1.08637

0.696491

1.1928

0.668162

1.64212

0.020852

2

2.7

109883.9

5.49

1

0.199

0.944075

0.800231

0.807777

0.307196

1.56886

0.142323

1.07095

0.803581

1

1

8.1

15797.53

10.56

0

0.644

0.831154

0.531129

1.11317

0.608567

1.34555

0.395049

1.50913

0.067166

3

3

8.2

56791.76

6.13

0

0.395

0.922848

0.746536

1.01163

0.960437

0.505178

0.098089

0.641915

0.106588

1

1

5.8

21430.77

8.26

2

0.118

0.874364

0.628767

0.903948

0.608516

0.980059

0.858161

0.820623

0.416237

1

1

5.0

45975.02

6.67

0

0.185

0.830484

0.529678

1.35622

0.105419

0.982215

0.863422

1.26781

0.337374

2

1

2.1

90287.03

8.3

0

0.448

1.17094

0.70114

1.16038

0.467156

0.821102

0.5012

0.841831

0.472795

1

1

2.0

63409.21

7.48

0

0.143

0.893039

0.673217

0.885934

0.543504

1.07478

0.918177

0.927033

0.736744

1

1

5.7

24000.53

9.52

0

0.297

0.920219

0.739965

0.772657

0.227441

0.613558

0.187688

0.596862

0.069433

1

1

2.4

50938.94

5.75

0

0.441

1.28772

0.495271

0.941267

0.752988

2.15517

0.002026

2.56536

1.67E08

1

1

1.2

107161.2

4.87

0

0.35

0.902696

0.696672

0.964111

0.846324

0.941675

0.76572

0.906537

0.668647

8

6

9.9

85337.9

7.06

0

0.087

0.977545

0.886747

0.970732

0.873849

1.03514

0.993949

1.37038

0.183628

16

4

21.5

22540.68

8.58

0

0.33

0.862773

0.601829

0.811853

0.317525

1.26605

0.528066

0.987844

0.949219

1

1

1.7

80253.05

6.04

0

0.363

0.959732

0.840464

0.949952

0.78813

0.879387

0.623066

0.970932

0.889083

1

1

5.1

35260.25

5.4

0

0.391

1.39709

0.336444

1.23781

0.280227

0.689659

0.279696

0.688545

0.160086

7

5

5.0

96417.46

5.4

0

0.548

0.857157

0.588964

0.933015

0.720068

1.35303

0.383664

1.44873

0.106854

2

2

2.9

73271.15

8.29

0

0.264

0.930439

0.765611

0.980725

0.915671

1.12038

0.819138

0.985664

0.941445

8

5

6.4

97251.64

5.95

0

0.457

0.979821

0.892691

0.77213

0.226368

1.00363

0.916001

0.858329

0.519565

4

3

8.8

53308.31

5.07

0

0.422

0.895583

0.679367

1.03826

0.864276

0.771279

0.408007

0.901353

0.651821

21

8

18.4

59520.23

8.12

0

0.213

0.932521

0.770869

1.16884

0.443877

0.9443

0.771952

1.3411

0.220975

8

4

26.7

21597.79

4.45

1

0.598

0.975255

0.88077

1.19673

0.372031

0.967655

0.828008

1.30578

0.272881

15

10

23.0

58529.98

5.58

0

0.318

0.904459

0.700984

0.970149

0.871419

1.06965

0.929424

1.30923

0.267473

1

1

1.7

59169.13

6.8

0

0.1

1.00114

0.948626

0.680228

0.089865

1.2748

0.512389

0.817518

0.408305

2

2

9.7

23317.21

6.24

0

0.584

0.966261

0.857374

0.9866

0.940372

1.09505

0.873904

1.03497

0.905422

15

7

12.5

74248

6.34

0

0.35

0.886651

0.657873

0.960285

0.830502

1.35385

0.38243

1.32384

0.245384

28

15

32.4

57817.17

6.63

0

0.093

0.925064

0.752089

0.945579

0.770377

1.11611

0.828311

1.23462

0.401146

20

6

29.8

24084.99

6.31

0

0.355

0.945209

0.803129

0.96534

0.851422

0.967898

0.828598

0.961885

0.857151

50

19

32.8

68735.18

6.32

0

0.414

0.910006

0.714621

0.779666

0.242045

0.844292

0.54814

0.622505

0.089001

7.5

1

1

0.8

1

1

3

60805.1

43

(continued on next page)

No. of Pages 73

KPYM_RAT

0

3

NSC 16186

GRIK5_RAT

6.32

4

22 April 2015

D4AB17_RAT

Sulfite oxidase OS = Rattus norvegicus GN = Suox PE = 4 SV = 1 Protein Pfas OS = Rattus norvegicus GN = Pfas PE = 4 SV = 1 Glutamate receptor ionotropic, kainate 5 OS = Rattus norvegicus GN = Grik5 PE = 1 SV = 1 Eph receptor B2 OS = Rattus norvegicus GN = Ephb2 PE = 2 SV = 1 60S ribosomal protein L27 OS = Rattus norvegicus GN = Rpl27 PE = 2 SV = 2 Cytoplasmic dynein 1 light intermediate chain 1 OS = Rattus norvegicus GN = Dync1li1 PE = 1 SV = 1 Receptor expression-enhancing protein 5 OS = Rattus norvegicus GN = Reep5 PE = 1 SV = 1 Fumarylacetoacetase OS = Rattus norvegicus GN = Fah PE = 1 SV = 1 Diacylglycerol kinase beta OS = Rattus norvegicus GN = Dgkb PE = 2 SV = 1 Protein Tbc1d24 OS = Rattus norvegicus GN = Tbc1d24 PE = 4 SV = 1 Protein Mrpl48 (Fragment) OS = Rattus norvegicus GN = Mrpl48 PE = 2 SV = 1 Tubulin gamma chain (Fragment) OS = Rattus norvegicus GN = LOC688197 PE = 3 SV = 1 General vesicular transport factor p115 OS = Rattus norvegicus GN = Uso1 PE = 1 SV = 1 6-phosphofructokinase, liver type OS = Rattus norvegicus GN = Pfkl PE = 2 SV = 3 RAB10, member RAS oncogene family OS = Rattus norvegicus GN = Rab10 PE = 2 SV = 1 Neurolysin, mitochondrial OS = Rattus norvegicus GN = Nln PE = 1 SV = 1 Calcineurin-like phosphoesterase domain-containing protein 1 OS = Rattus norvegicus GN = Cpped1 PE = 2 SV = 1 Heat shock protein 105 kDa OS = Rattus norvegicus GN = Hsph1 PE = 1 SV = 1 Pck2 protein (Fragment) OS = Rattus norvegicus GN = Pck2 PE = 2 SV = 1 Dipeptidyl aminopeptidase-like protein 6 OS = Rattus norvegicus GN = Dpp6 PE = 2 SV = 1 Carboxypeptidase E OS = Rattus norvegicus GN = Cpe PE = 1 SV = 1 Amine oxidase [flavin-containing] A OS = Rattus norvegicus GN = Maoa PE = 4 SV = 1 Membrane-associated progesterone receptor component 1 OS = Rattus norvegicus GN = Pgrmc1 PE = 1 SV = 3 Serine/threonine-protein phosphatase OS = Rattus norvegicus GN = Ppp3ca PE = 2 SV = 1 Protein Gpr123 OS = Rattus norvegicus GN = Gpr123 PE = 2 SV = 1 Ras-related protein Ral-B OS = Rattus norvegicus GN = Ralb PE = 2 SV = 1 Dihydropyrimidinase-related protein 1 OS = Rattus norvegicus GN = Crmp1 PE = 2 SV = 1 Pyruvate kinase isozymes M1/M2 OS = Rattus norvegicus GN = Pkm PE = 1 SV = 3 Protein Rab2b OS = Rattus norvegicus GN = Rab2b PE = 2 SV = 1 Isoform 2 of Syntaxin-binding protein 1 OS = Rattus norvegicus GN = Stxbp1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

G3V6R5_RAT

GDIA_RAT D3ZHB3_RAT TIM16_RAT

D3ZH36_RAT B0BN52_RAT NRP2_RAT

D3ZFQ8_RAT D3ZL50_RAT F1LU71_RAT E9PTI1_RAT D3ZV92_RAT F1LM31_RAT B1WBX6_RAT CYTC_RAT TCPE_RAT PP2AB_RAT

MYL6_RAT NMT1_RAT RAB21_RAT F1LP05_RAT KCMA1_RAT

D3ZW49_RAT DHSA_RAT

94785.98

6.06

0

0.462

0.891399

0.669265

0.889121

0.554751

1.03951

0.995738

0.890122

0.615977

9 61

6 15

5.8 36.7

170247.7 48395.57

6.08 9.16

0 0

0.325 0.067

0.911834 0.912213

0.719137 0.720072

0.76388 1.05203

0.210049 0.815272

1.07625 1.0719

0.91495 0.924479

0.887028 1.28502

0.606258 0.307022

46

20

29.7

60954.79

5.91

0

0.085

0.951953

0.820416

1.26426

0.230038

1.09461

0.874854

1.27873

0.317898

13

8

21.5

50536.08

5

0

0.303

0.841474

0.553734

1.359

0.102728

0.594425

0.168543

1.00469

0.992416

5

3

29.9

15219.67

8.81

0

0.159

0.878208

0.637813

1.03038

0.892601

0.9122

0.696863

0.803112

0.372698

1

1

12.9

13730.3

6.29

0

0.502

0.865579

0.608301

0.714084

0.129279

0.921747

0.718926

0.683328

0.153246

1

1

1.6

89829.92

7.11

0

0.282

0.848722

0.569888

0.997737

0.987342

0.700292

0.294655

0.712854

0.195024

14

4

15.7

32244.4

8.87

0

0.293

1.08609

0.867265

1.18076

0.412232

1.00724

0.924902

1.54286

0.050899

2

1

1.1

102603.3

5.29

0

0.472

1.03045

0.980008

0.842854

0.403438

0.779831

0.423228

0.817988

0.4095

6

5

10.5

71346.29

8.77

1

0.015

0.98219

0.898885

0.988504

0.948393

0.918643

0.711725

1.05331

0.853221

36

6

25.2

35434.43

9.33

0

0.115

0.958259

0.836659

0.875813

0.508559

0.8516

0.563369

0.871218

0.557699

0

0.178462

0.251

1.04226

0.70771

0.1872

18

9

24.6

33138.25

9.49

0

0.056

0.975277

0.88083

1.54146

0.013786

1.08623

0.893129

1.50442

0.069745

3

3

8.5

55868.47

6.18

0

0.368

0.863176

0.602755

0.922485

0.678805

1.25716

0.544252

1.30489

0.27429

5

3

4.0

6.11

0

0.269

0.899184

0.688107

0.787021

0.258068

1.46185

0.241326

1.03286

0.911463

1

1

2.5

53310.83

5.85

0

0.226

0.854411

0.582722

1.20887

0.34314

0.86809

0.598465

1.33487

0.229566

1

1

3.0

46493.16

9.01

0

0.426

1.06102

0.917874

1.17874

0.417501

0.680813

0.267652

0.882768

0.59299

3

3

27.1

15436.55

9.35

0

0.27

1.04891

0.942439

1.00993

0.966583

1.04906

0.974706

1.03854

0.895222

9

6

10.0

59536.14

5.51

0

0.17

0.908716

0.711443

0.811909

0.317669

0.987552

0.876477

0.92232

0.720877

7

4

15.5

35574.71

5.21

0

0.446

0.87321

0.626063

1.08038

0.716792

1.09415

0.875851

1.27906

0.317311

3

2

18.5

16974.98

4.46

0

0.406

0.862101

0.600282

0.687342

0.097224

1.14172

0.77365

0.844826

0.481108

1

1

2.2

56859.74

8.04

0

0.507

1.02573

0.989625

0.811769

0.317311

0.618657

0.193051

0.749368

0.257531

2

2

9.9

24163.11

8.11

0

0.343

1.06748

0.904784

1.02458

0.913507

1.43515

0.272234

1.43284

0.119914

174

32

51.2

59811.98

9.29

0

0.096

0.933751

0.773979

1.08241

0.709874

0.942985

0.768828

1.04003

0.890954

2

1

0.8

138386.1

6.98

0

0.077

0.909744

0.713976

0.755553

0.194462

0.861202

0.583685

0.717528

0.20234

16

11

10.8

105690.6

5.19

0

0.088

0.945684

0.804341

0.795054

0.276393

1.02564

0.970399

0.937847

0.773565

1

1

7.0

22639.25

8.51

0

0.014

0.968925

0.864292

0.680851

0.090491

0.789617

0.441046

0.622483

0.088982

24

13

22.9

71614.43

6.75

0

0.254

0.912922

0.721827

0.981447

0.918702

0.955183

0.797945

0.955936

0.836277

1

1

0.7

175157.5

104007.2

6.52

0.95596

1.12359

0.575782

0.604529

No. of Pages 73

Q3ZB97_RAT

2.7

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Q6GMM8_RAT

2

NSC 16186

CH60_RAT

2

22 April 2015

NRX3A_RAT QCR2_RAT

AMP deaminase 2 OS = Rattus norvegicus GN = Ampd2 PE = 2 SV = 2 Isoform 8 of Neurexin-3 OS = Rattus norvegicus GN = Nrxn3 Cytochrome b-c1 complex subunit 2, mitochondrial OS = Rattus norvegicus GN = Uqcrc2 PE = 1 SV = 2 60 kDa heat shock protein, mitochondrial OS = Rattus norvegicus GN = Hspd1 PE = 1 SV = 1 Rab GDP dissociation inhibitor alpha OS = Rattus norvegicus GN = Gdi1 PE = 1 SV = 1 40S ribosomal protein S12 OS = Rattus norvegicus GN = LOC100360573 PE = 3 SV = 1 Mitochondrial import inner membrane translocase subunit TIM16 OS = Rattus norvegicus GN = Magmas-ps1 PE = 3 SV = 1 Protein Elfn2 OS = Rattus norvegicus GN = Elfn2-ps1 PE = 4 SV = 1 Protein Mtch2 OS = Rattus norvegicus GN = Mtch2 PE = 2 SV = 1 Neuropilin-2 OS = Rattus norvegicus GN = Nrp2 PE = 2 SV = 1 Long-chain fatty acid transport protein 1 OS = Rattus norvegicus GN = Slc27a1 PE = 2 SV = 1 Cytochrome c-1 (Predicted), isoform CRA_c OS = Rattus norvegicus GN = Cyc1 PE = 4 SV = 1 Protein Ttc37 OS = Rattus norvegicus GN = Ttc37 PE = 4 SV = 1 Protein Auh (Fragment) OS = Rattus norvegicus GN = Auh PE = 3 SV = 1 Protein Atp6v1h OS = Rattus norvegicus GN = Atp6v1h PE = 4 SV = 1 Protein Epha4 OS = Rattus norvegicus GN = Epha4 PE = 2 SV = 1 Uncharacterized protein (Fragment) OS = Rattus norvegicus PE = 2 SV = 1 Smap2 protein OS = Rattus norvegicus GN = Smap2 PE = 2 SV = 1 Cystatin-C OS = Rattus norvegicus GN = Cst3 PE = 1 SV = 2 T-complex protein 1 subunit epsilon OS = Rattus norvegicus GN = Cct5 PE = 1 SV = 1 Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform OS = Rattus norvegicus GN = Ppp2cb PE = 1 SV = 1 Myosin light polypeptide 6 OS = Rattus norvegicus GN = Myl6 PE = 1 SV = 3 Glycylpeptide N-tetradecanoyltransferase 1 OS = Rattus norvegicus GN = Nmt1 PE = 2 SV = 1 Ras-related protein Rab-21 OS = Rattus norvegicus GN = Rab21 PE = 2 SV = 1 ATP synthase subunit alpha OS = Rattus norvegicus GN = Atp5a1 PE = 2 SV = 1 Isoform 4 of Calcium-activated potassium channel subunit alpha-1 OS = Rattus norvegicus GN = Kcnma1 Adaptor-related protein complex 2, beta 1 subunit, isoform CRA_b OS = Rattus norvegicus GN = Ap2b1 PE = 2 SV = 1 Protein Tmem9b OS = Rattus norvegicus GN = Tmem9b PE = 4 SV = 1 Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial OS = Rattus norvegicus GN = Sdha PE = 1 SV = 1

44

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

AMPD2_RAT

LGI1_RAT D3ZRN5_RAT TRFE_RAT G3V734_RAT D4ADE8_RAT GRPE1_RAT CDV3_RAT MOG_RAT F1LTJ9_RAT KCC2D_RAT

D3ZD09_RAT D4A197_RAT Q6JBI6_RAT Q4FZZ4_RAT Q5XIJ3_RAT C1QBP_RAT

F1MA38_RAT ABI1_RAT FAS_RAT D3ZWW5_RAT ZNT3_RAT PDIA3_RAT CDC42_RAT

SCOT1_RAT

9.2

31907.05

5.97

0

0.739

0.935141

0.7775

0.855931

0.443501

0.779861

0.423282

0.796644

0.357356

6

2

9.2

27414.05

5.68

0

0.256

1.01072

0.973849

1.25431

0.248111

0.725726

0.332576

1.31585

0.257294

15

8

15.5

85558.99

8.23

0

0.191

0.896757

0.682212

0.978569

0.906622

0.712184

0.312008

0.878232

0.579006

7

6

11.0

63727.2

8.26

0

0.18

0.911467

0.718227

0.829722

0.365468

1.37071

0.35759

1.4198

0.131537

1

1

3.4

60042.01

8.3

0

0.166

0.621385

0.186961

0.753231

0.19027

1.62782

0.103098

1.20329

0.467567

6

6

8.6

76394.38

7.14

0

0.252

0.883905

0.65132

1.04783

0.830149

1.14716

0.762182

1.36235

0.193374

3

2

9.6

36132.31

9.08

0

0.005

0.908374

0.710599

1.34163

0.120508

1.07943

0.907979

0.705019

0.183201

5

3

7.1

73144.6

6.73

0

0.487

0.754316

0.378722

1.29562

0.17924

0.612325

0.186407

0.665481

0.131522

2

1

7.8

24296.74

8.57

0

0.511

0.869246

0.616809

1.03127

0.889376

0.955356

0.798361

1.12425

0.659128

2

1

12.7

24309.83

5.7

0

1.117

1.40856

0.321933

1.2034

0.355979

1.81599

0.031582

1.40605

0.144722

19

8

33.5

27881.21

8.61

2

0.096

0.938577

0.786221

0.682138

0.091795

0.92447

0.725262

0.733899

0.229534

2

2

4.1

59184.63

6.21

0

0.492

0.905547

0.703652

1.05389

0.808685

0.795985

0.452868

0.869437

0.552348

17

7

15.3

57708.48

7.61

0

0.4

0.982516

0.899739

1.22507

0.30689

0.949376

0.784046

1.32261

0.247183

9

3

37.2

10071.35

8.96

0

0.764

0.922031

0.744492

1.39114

0.075377

1.17722

0.699765

1.87299

0.001666

2

1

7.3

18815.55

8.95

0

0.083

0.814298

0.49524

1.15925

0.470296

0.696028

0.288592

0.979213

0.91847

1

1

1.3

5.9

0

0.953

1.34747

0.403983

0.972369

0.880676

1.01793

0.951324

0.763299

0.284699

40

16

32.1

43215.19

8.49

0

0.287

0.950106

0.815673

1.26037

0.236984

0.921228

0.717721

1.17261

0.538089

14

8

24.2

42849.99

9.17

0

0.087

0.949293

0.813587

1.25021

0.255845

0.956548

0.80122

1.26675

0.339295

1

1

2.2

30996.55

4.77

0

0.441

0.959203

0.839097

1.12276

0.578353

0.982424

0.863933

1.03402

0.908133

6

3

7.4

67413.51

4.6

0

0.781

1.23357

0.586644

1.18928

0.390481

0.486163

0.086662

0.806608

0.381156

2

2

5.3

51704.14

6.57

0

0.679

0.790503

0.446868

1.00682

0.977875

0.806961

0.473657

0.727556

0.218704

5

5

2.6

5.96

0

0.063

0.777051

0.420757

0.960553

0.831608

1.20276

0.648278

1.18918

0.49935

2

2

3.9

62683.57

8.72

0

0.12

0.87735

0.63579

1.15693

0.476827

0.909963

0.691731

1.16996

0.544413

3

3

10.6

41897.94

6.83

6

0.218

0.908095

0.709912

0.795653

0.277796

1.01501

0.944106

1.11175

0.692111

8

5

12.1

56622.69

5.88

0

0.455

0.919153

0.737306

1.0639

0.773563

1.012

0.936647

1.33042

0.23586

3

2

11.0

21258.36

6.16

0

0.157

1.14491

0.75101

0.708992

0.122614

1.07478

0.918178

1.08987

0.751244

11

9

12.3

95584.02

5.86

0

0.463

0.933897

0.77435

0.71573

0.131495

0.853899

0.568203

0.620033

0.08694

8

4

5.4

56203.22

8.7

0

0.115

0.895617

0.679449

0.830929

0.368862

0.896306

0.660704

0.850132

0.496033

156646.7

272646.7

(continued on next page)

45

No. of Pages 73

DLG2_RAT

2

NSC 16186

K6PF_RAT

3

22 April 2015

PCSK1_RAT

Phosphatidylinositol transfer protein alpha isoform OS = Rattus norvegicus GN = Pitpna PE = 1 SV = 2 ProSAAS OS = Rattus norvegicus GN = Pcsk1n PE = 1 SV = 1 6-phosphofructokinase, muscle type OS = Rattus norvegicus GN = Pfkm PE = 2 SV = 3 Leucine-rich glioma-inactivated protein 1 OS = Rattus norvegicus GN = Lgi1 PE = 1 SV = 1 Protein Trove2 OS = Rattus norvegicus GN = Trove2 PE = 4 SV = 1 Serotransferrin OS = Rattus norvegicus GN = Tf PE = 1 SV = 3 2,4-dienoyl CoA reductase 1, mitochondrial, isoform CRA_a OS = Rattus norvegicus GN = Decr1 PE = 4 SV = 1 Protein Ddx3x OS = Rattus norvegicus GN = Ddx3x PE = 3 SV = 1 GrpE protein homolog 1, mitochondrial OS = Rattus norvegicus GN = Grpel1 PE = 1 SV = 2 Protein CDV3 homolog OS = Rattus norvegicus GN = Cdv3 PE = 2 SV = 1 Myelin-oligodendrocyte glycoprotein OS = Rattus norvegicus GN = Mog PE = 1 SV = 1 Protein LOC100364190 (Fragment) OS = Rattus norvegicus GN = LOC100364190 PE = 2 SV = 1 Isoform Delta 3 of Calcium/calmodulin-dependent protein kinase type II subunit delta OS = Rattus norvegicus GN = Camk2d Cytochrome c oxidase subunit 6B1 OS = Rattus norvegicus GN = Cox6b1 PE = 4 SV = 1 Methylmalonyl CoA epimerase (Predicted), isoform CRA_d OS = Rattus norvegicus GN = Mcee PE = 4 SV = 1 LMO7b OS = Rattus norvegicus GN = Lmo7 PE = 2 SV = 1 Protein LOC100365902 OS = Rattus norvegicus GN = LOC100365902 PE = 2 SV = 1 Isocitrate dehydrogenase 3 (NAD), gamma OS = Rattus norvegicus GN = Idh3g PE = 2 SV = 1 Complement component 1 Q subcomponent-binding protein, mitochondrial OS = Rattus norvegicus GN = C1qbp PE = 1 SV = 2 Calnexin OS = Rattus norvegicus GN = Canx PE = 2 SV = 1 Abl interactor 1 OS = Rattus norvegicus GN = Abi1 PE = 2 SV = 3 Fatty acid synthase OS = Rattus norvegicus GN = Fasn PE = 1 SV = 3 Protein Slc30a9 OS = Rattus norvegicus GN = Slc30a9 PE = 4 SV = 1 Zinc transporter 3 OS = Rattus norvegicus GN = Slc30a3 PE = 2 SV = 1 Protein disulfide-isomerase A3 OS = Rattus norvegicus GN = Pdia3 PE = 1 SV = 2 Cell division control protein 42 homolog OS = Rattus norvegicus GN = Cdc42 PE = 1 SV = 2 Isoform 2 of Disks large homolog 2 OS = Rattus norvegicus GN = Dlg2 Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial OS = Rattus norvegicus GN = Oxct1 PE = 1 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

PIPNA_RAT

CACP_RAT RAP2B_RAT DPYL3_RAT CYB5_RAT D3Z994_RAT D4A1U9_RAT TCPA_RAT

E41L1_RAT RB11A_RAT D3ZQ57_RAT ATP5L_RAT RS20_RAT TPIS_RAT Q5XIM0_RAT SYPH_RAT B5DFI9_RAT NIT2_RAT ECHM_RAT F1LTW5_RAT Q8SEZ1_RAT Q499R7_RAT D3ZQE0_RAT F1LN61_RAT

D3ZHI9_RAT D4A4Q4_RAT

44764.87

8.47

0

0.146

1.00937

0.970302

1.07983

0.718642

1.00511

0.919654

1.35731

0.199676

2

1

9.7

16312.74

6.73

0

0.235

0.750918

0.37267

1.11324

0.608341

0.693387

0.284881

0.935129

0.764258

1

1

1.1

6.03

0

0.497

0.822638

0.512835

0.837051

0.386377

0.867032

0.596183

0.958311

0.844594

3

3

4.5

70799.93

8.73

0

0.25

0.927863

0.759123

1.32287

0.142316

1.38581

0.336213

1.51897

0.062029

8

4

26.8

20504.14

4.73

0

0.202

0.835872

0.541405

1.02046

0.928417

0.995616

0.896266

0.909498

0.678332

5

3

4.7

73898.48

6.03

0

0.398

0.873177

0.625986

0.930215

0.709011

0.966463

0.825123

0.937743

0.77321

6

3

34.0

11481.56

5.42

0

1.017

0.862132

0.600354

0.942891

0.759525

1.02933

0.979549

1.14499

0.605868

1

1

1.8

50791.98

6.19

0

0.511

1.15239

0.736563

0.922203

0.677712

1.09512

0.873745

1.00776

0.983562

10

4

6.9

34944.29

8.78

0

0.594

0.945951

0.805025

0.815134

0.326004

1.15848

0.738474

1.22266

0.425801

7

6

12.8

60358.97

5.86

0

0.018

0.949643

0.814483

0.740341

0.168204

1.15846

0.738508

1.03931

0.893012

3

3

2.9

140792.4

8.84

0

0.45

0.945704

0.804393

0.864991

0.47254

0.92835

0.734325

0.916844

0.702593

5

4

3.4

171009

5.23

0

0.799

0.885855

0.655972

0.76267

0.20773

0.745685

0.364445

0.598645

0.070669

1

1

5.1

6.12

0

0.421

1.28085

0.50643

1.07126

0.748046

1.6087

0.114749

2.09811

7.60E05

3

3

3.1

5.73

0

0.366

0.949909

0.815166

0.95428

0.805811

0.770052

0.40585

0.739166

0.238812

6

4

35.0

11433.31

9.57

0

0.243

0.975774

0.882125

1.05774

0.795136

0.857791

0.576428

1.01351

0.967026

3

3

22.7

13372.56

9.95

0

0.396

0.897872

0.684917

0.767006

0.21613

1.01966

0.955609

0.971113

0.889722

29

11

56.6

26848.61

6.89

0

0.1

0.884622

0.653031

1.03377

0.880401

0.791628

0.44476

1.06182

0.829185

3

3

7.7

47392.62

8.3

0

0.2

1.06067

0.91858

1.17811

0.419161

0.526502

0.1123

1.02883

0.923014

10

3

9.6

33949.13

4.83

0

0.045

0.882774

0.648631

0.78631

0.256489

1.01563

0.945629

0.910204

0.680651

3

3

11.1

47943.47

8.88

0

0.419

0.853426

0.580492

1.00861

0.971381

0.748121

0.368462

0.967239

0.876021

2

2

10.5

30700.63

6.9

0

0.285

0.804942

0.475895

0.654689

0.067061

0.851148

0.562421

0.710931

0.192072

6

6

22.4

31516.07

8.4

0

0.104

1.03964

0.961293

1.0105

0.964528

0.758126

0.385245

1.08498

0.764682

1

1

0.9

7.26

0

0.198

0.735704

0.34631

0.946616

0.774577

0.787773

0.437656

0.848649

0.491837

1

1

13.0

13086.43

4.5

3

0.792

0.986444

0.910023

0.859376

0.454422

1.02512

0.969117

0.734963

0.231387

1

1

3.3

37676.39

6.41

0

0.561

0.947245

0.808337

1.73415

0.000836

1.04099

0.992476

1.34575

0.214697

7

4

11.4

33167.4

6.66

0

0.381

0.94463

0.801648

0.713937

0.129084

1.07809

0.910915

0.902043

0.65405

8

7

20.1

36825.25

7.24

0

0.349

0.795506

0.45681

1.18365

0.404784

1.18736

0.67915

1.49684

0.07407

16

8

7.0

5.93

0

0.005

0.905359

0.703192

0.887676

0.549638

0.873313

0.609784

0.714248

0.197185

1

1

2.1

50065.58

5.52

0

0.181

0.846549

0.565023

1.0829

0.708212

0.852598

0.565464

1.09271

0.743471

5

4

24.0

17037.46

9.41

0

0.217

0.852814

0.579106

0.931187

0.71284

1.03284

0.988256

1.01947

0.949881

130185.3

24393.23 154410.7

139003.7

123562.1

No. of Pages 73

S12A5_RAT

2.2

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

CLAP2_RAT

1

NSC 16186

TCPR1_RAT

3

22 April 2015

D4A807_RAT

Short-chain specific acyl-CoA dehydrogenase, mitochondrial OS = Rattus norvegicus GN = Acads PE = 1 SV = 2 Protein Selm OS = Rattus norvegicus GN = Selm PE = 4 SV = 1 Tectonin beta-propeller repeat-containing protein 1 OS = Rattus norvegicus GN = Tecpr1 PE = 2 SV = 1 Carnitine O-acetyltransferase OS = Rattus norvegicus GN = Crat PE = 1 SV = 1 Ras-related protein Rap-2b OS = Rattus norvegicus GN = Rap2b PE = 2 SV = 1 Isoform 2 of Dihydropyrimidinase-related protein 3 OS = Rattus norvegicus GN = Dpysl3 D4A1G4_RAT Cytochrome b5 OS = Rattus norvegicus GN = Cyb5a PE = 2 SV = 1 Protein Tbc1d22a OS = Rattus norvegicus GN = Tbc1d22a PE = 4 SV = 1 Leukocyte surface antigen CD47 OS = Rattus norvegicus GN = Cd47 PE = 2 SV = 1 T-complex protein 1 subunit alpha OS = Rattus norvegicus GN = Tcp1 PE = 1 SV = 1 CLIP-associating protein 2 OS = Rattus norvegicus GN = Clasp2 PE = 2 SV = 1 Isoform L of Band 4.1-like protein 1 OS = Rattus norvegicus GN = Epb41l1 Ras-related protein Rab-11A OS = Rattus norvegicus GN = Rab11a PE = 1 SV = 3 Protein Plxnb2 OS = Rattus norvegicus GN = Plxnb2 PE = 2 SV = 1 ATP synthase subunit g, mitochondrial OS = Rattus norvegicus GN = Atp5l PE = 1 SV = 2 40S ribosomal protein S20 OS = Rattus norvegicus GN = Rps20 PE = 3 SV = 1 Triosephosphate isomerase OS = Rattus norvegicus GN = Tpi1 PE = 1 SV = 2 BCS1-like (Yeast) OS = Rattus norvegicus GN = Bcs1l PE = 2 SV = 1 Synaptophysin (Fragment) OS = Rattus norvegicus GN = Syp PE = 4 SV = 1 Pdk3 protein OS = Rattus norvegicus GN = Pdk3 PE = 2 SV = 1 Omega-amidase NIT2 OS = Rattus norvegicus GN = Nit2 PE = 1 SV = 1 Enoyl-CoA hydratase, mitochondrial OS = Rattus norvegicus GN = Echs1 PE = 1 SV = 1 Protein Tanc2 (Fragment) OS = Rattus norvegicus GN = Tanc2 PE = 2 SV = 1 NADH-ubiquinone oxidoreductase chain 3 OS = Rattus norvegicus GN = Mt-nd3 PE = 3 SV = 1 Ppa1 protein (Fragment) OS = Rattus norvegicus GN = Ppa1 PE = 2 SV = 1 Sodium/potassium-transporting ATPase subunit beta-2 OS = Rattus norvegicus GN = Atp1b2 PE = 2 SV = 1 Uncharacterized protein (Fragment) OS = Rattus norvegicus PE = 2 SV = 1 Isoform 2 of Solute carrier family 12 member 5 OS = Rattus norvegicus GN = Slc12a5 Protein Ppp2r5e (Fragment) OS = Rattus norvegicus GN = Ppp2r5e PE = 2 SV = 1 Protein LOC100365923 OS = Rattus norvegicus GN = Ociad2 PE = 4 SV = 1

46

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

ACADS_RAT

ATX10_RAT TAGL3_RAT Q63629_RAT G3V6G7_RAT CD59_RAT D3ZUY8_RAT B5DEL8_RAT

F1LX07_RAT RAP1B_RAT CXA1_RAT RAP1A_RAT THY1_RAT Q9QXU3_RAT F1LNF7_RAT CX6A1_RAT NPTX1_RAT DHSD_RAT

Q6IN22_RAT F1LZ51_RAT EFTU_RAT FABP5_RAT PDIA1_RAT VDAC1_RAT

Q6IE71_RAT TXTP_RAT

16.3

57541.27

8.97

0

0.615

0.86636

0.61011

1.14833

0.501431

0.924398

0.725095

1.01933

0.950294

1

1

2.8

36397.71

9.45

0

0.218

0.826518

0.521128

0.995316

0.977125

1.02811

0.976536

0.999905

0.992305

6

3

14.6

27245.25

8.91

0

0.243

1.00234

0.951785

1.12444

0.573146

0.953866

0.794787

1.35498

0.202645

1

1

3.0

53726.24

5.02

0

0.142

0.826838

0.521817

0.858789

0.452548

0.875172

0.613836

0.888853

0.611983

4

3

21.1

22500.46

6.84

0

0.58

0.96592

0.856489

0.979139

0.909012

1.12532

0.808544

1.27996

0.315743

2

2

6.0

48133.15

8.89

0

0.624

0.925553

0.753316

1.0294

0.896118

0.889308

0.645025

0.975985

0.906997

1

1

1.2

85896.92

8.42

0

0.144

0.862292

0.600721

0.845124

0.41023

0.989205

0.880528

0.859954

0.524298

3

2

16.7

13790.15

8.9

2

0.342

0.949183

0.813304

0.853564

0.436085

1.11912

0.821839

1.11245

0.690251

14

9

8.8

6.66

0

0.078

0.879864

0.641728

0.985207

0.934511

0.88843

0.64307

1.04898

0.865483

11

6

50.0

12699.63

9.1

0

0.9

0.877619

0.636424

1.26723

0.224819

0.873836

0.610923

0.936961

0.770529

42

7

37.2

25737.49

9.56

0

0.026

0.823503

0.514678

1.00152

0.99714

0.971038

0.836209

1.06359

0.824207

6

4

25.5

20797.53

5.65

0

0.375

0.902609

0.696459

0.900554

0.596006

1.15737

0.740787

1.23658

0.397194

107673.8

23

4

13.1

43030.92

8.97

0

0.22

0.820781

0.508889

0.630573

0.050126

0.770195

0.406102

0.5946

0.067891

5

3

18.5

20986.96

6.39

0

0.375

0.871181

0.621318

0.937467

0.737767

0.947442

0.779432

1.04958

0.863781

12

5

21.7

18171.96

9.42

0

0.019

0.866988

0.611564

0.880914

0.526025

1.15077

0.754603

0.999887

0.992242

2

2

11.7

31062.94

6.16

1

0.369

0.845261

0.562148

0.656256

0.068307

0.793689

0.448585

0.573111

0.054604

33

12

28.1

39582.23

6.46

0

0.068

0.904473

0.701021

0.909553

0.629428

0.87885

0.621888

1.06161

0.829784

1

1

14.4

12300.9

9.3

0

0.338

0.941496

0.79365

0.866785

0.478414

0.965372

0.822485

0.974517

0.901788

5

4

12.5

47215.85

6.29

0

0.414

0.971065

0.869856

0.955395

0.810382

0.696307

0.288987

0.876061

0.572371

1

1

5.0

16975.55

9.42

0

0.389

1.58703

0.14812

0.752646

0.189224

1.10369

0.855139

1.11261

0.689823

5

3

11.2

37543.74

5.47

0

-0.345

0.887111

0.658974

1.30062

0.171975

0.868423

0.599184

1.20618

0.461194

1

1

21.2

13101.77

6.15

0

0.517

0.75431

0.378711

1.22285

0.311691

0.955492

0.798686

1.44059

0.113396

33

13

31.9

49521.81

7.23

0

0.179

0.909824

0.714174

0.841373

0.399039

0.813787

0.486848

0.902396

0.655192

2

2

21.5

15059.24

6.73

0

0.367

0.84552

0.562724

1.08154

0.712847

0.82118

0.501354

1.07919

0.780661

7

5

11.0

56950.63

4.82

0

0.382

0.830424

0.529549

0.882343

0.530969

1.18228

0.689436

1.17102

0.541893

54

18

63.6

30755.12

8.62

0

0.423

0.82663

0.52137

0.847714

0.418067

1.02061

0.957962

1.06702

0.814588

2

1

5.5

20468.41

6.29

0

0.007

1.01151

0.975947

0.951382

0.793958

0.938414

0.758

1.15974

0.56919

1

1

1.4

80107.59

5.02

0

0.658

2.02832

0.010083

0.872821

0.498459

1.21163

0.630758

2.31926

1.98E06

3

2

7.1

33834.97

9.88

0

0.069

0.926083

0.754647

1.12281

0.578197

0.99091

0.884709

1.25483

0.361491

47

(continued on next page)

No. of Pages 73

VPS29_RAT

6

NSC 16186

HCD2_RAT

12

22 April 2015

F8WFF9_RAT

Isoform 2 of Brain-specific angiogenesis inhibitor 1-associated protein 2 OS = Rattus norvegicus GN = Baiap2 Leucine-rich repeat-containing protein 57 (Fragment) OS = Rattus norvegicus GN = Lrrc57 PE = 4 SV = 1 3-hydroxyacyl-CoA dehydrogenase type-2 OS = Rattus norvegicus GN = Hsd17b10 PE = 1 SV = 3 Ataxin-10 OS = Rattus norvegicus GN = Atxn10 PE = 1 SV = 1 Transgelin-3 OS = Rattus norvegicus GN = Tagln3 PE = 1 SV = 2 Centaurin alpha OS = Rattus norvegicus GN = Adap1 PE = 2 SV = 1 Polyribonucleotide nucleotidyltransferase 1 OS = Rattus norvegicus GN = Pnpt1 PE = 4 SV = 1 CD59 glycoprotein OS = Rattus norvegicus GN = Cd59 PE = 1 SV = 2 Adaptor protein complex AP-2, alpha 1 subunit (Predicted) OS = Rattus norvegicus GN = Ap2a1 PE = 4 SV = 1 NADH dehydrogenase (Ubiquinone) Fe-S protein 5 OS = Rattus norvegicus GN = LOC100361505 PE = 4 SV = 1 Protein Slc25a12 OS = Rattus norvegicus GN = Slc25a12 PE = 3 SV = 1 Ras-related protein Rap-1b OS = Rattus norvegicus GN = Rap1b PE = 2 SV = 2 Gap junction alpha-1 protein OS = Rattus norvegicus GN = Gja1 PE = 1 SV = 2 Ras-related protein Rap-1A OS = Rattus norvegicus GN = Rap1a PE = 1 SV = 1 Thy-1 membrane glycoprotein OS = Rattus norvegicus GN = Thy1 PE = 1 SV = 1 Sodium channel, voltage-gated, type I, beta, isoform CRA_b OS = Rattus norvegicus GN = Scn1b PE = 2 SV = 1 Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial OS = Rattus norvegicus GN = Idh3a PE = 2 SV = 1 Cytochrome c oxidase subunit 6A1, mitochondrial OS = Rattus norvegicus GN = Cox6a1 PE = 1 SV = 2 Neuronal pentraxin-1 OS = Rattus norvegicus GN = Nptx1 PE = 1 SV = 1 Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial OS = Rattus norvegicus GN = Sdhd PE = 2 SV = 1 Cathepsin B OS = Rattus norvegicus GN = Ctsb PE = 2 SV = 1 Protein RGD1565653 (Fragment) OS = Rattus norvegicus GN = RGD1565653 PE = 4 SV = 1 Elongation factor Tu, mitochondrial OS = Rattus norvegicus GN = Tufm PE = 1 SV = 1 Fatty acid-binding protein, epidermal OS = Rattus norvegicus GN = Fabp5 PE = 1 SV = 3 Protein disulfide-isomerase OS = Rattus norvegicus GN = P4hb PE = 1 SV = 2 Voltage-dependent anion-selective channel protein 1 OS = Rattus norvegicus GN = Vdac1 PE = 1 SV = 4 Vacuolar protein sorting-associated protein 29 OS = Rattus norvegicus GN = Vps29 PE = 1 SV = 2 Ubiquitin specific protease 11 OS = Rattus norvegicus GN = Usp11 PE = 2 SV = 1 Tricarboxylate transport protein, mitochondrial OS = Rattus norvegicus GN = Slc25a1 PE = 1 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

BAIP2_RAT

D3ZAN3_RAT G3P_RAT CNDP2_RAT Q4QQV0_RAT PP2BB_RAT

MPRD_RAT 1433E_RAT

B1WC64_RAT G6PI_RAT D3ZVQ0_RAT SSDH_RAT LPHN1_RAT D4A719_RAT F1LQX0_RAT O70511_RAT Q5BJX2_RAT SLK_RAT Q35737_RAT HS90A_RAT SCN2B_RAT RGS6_RAT Q68FQ9_RAT

EF1G_RAT VDAC2_RAT D3ZS58_RAT

18052.96

8.64

0

0.216

0.82277

0.513116

0.943781

0.763114

0.95713

0.80262

1.10825

0.70145

1

1

6.2

23115.04

5.79

0

0.223

0.790993

0.447838

0.821722

0.34347

0.702083

0.297227

0.661939

0.127509

2

2

7.2

34868.9

9.57

1

0.781

1.05651

0.92702

1.39564

0.072074

0.818909

0.496873

1.03198

0.913981

12

8

8.7

106902.8

5.69

0

0.337

0.885281

0.654601

0.952965

0.800427

0.814912

0.489041

1.00206

1

93

14

39.9

35827.59

8.14

0

0.089

0.850172

0.573147

0.913792

0.645445

0.975218

0.846364

1.19996

0.474953

1

1

2.5

52692.54

5.43

0

0.294

0.8736

0.626975

0.766958

0.216035

0.870649

0.603998

0.793124

0.349179

56

11

25.1

50058.83

4.8

0

0.344

0.87489

0.630002

1.32657

0.137786

1.10681

0.848375

1.69051

0.012942

9

6

13.3

59112.74

5.6

0

0.295

0.884982

0.653887

1.02618

0.907747

0.977277

0.851378

0.989627

0.955581

2

2

12.6

31095.03

5.25

1

0.16

1.1855

0.673795

1.13906

0.528692

1.40431

0.311168

0.863713

0.535329

28

10

38.4

29173.58

4.63

0

0.54

0.909003

0.712149

1.03832

0.864078

1.02622

0.971854

1.21842

0.434756

8

5

23.5

28398.69

8.21

0

0.299

0.814095

0.494816

0.966479

0.856148

1.09373

0.87676

1.16128

0.565418

2

2

4.4

56699.31

9.16

0

0.201

0.906357

0.705641

1.28937

0.188633

0.986327

0.873479

1.12652

0.653196

14

6

9.5

62826.24

7.38

0

0.285

0.812681

0.491868

1.0159

0.944948

0.658833

0.239283

1.04921

0.864831

2

2

2.3

95778.06

4.89

0

0.436

0.839305

0.548944

0.912276

0.639699

0.876159

0.615993

1.00742

0.984559

18

10

21.2

56130.7

8.35

0

0.036

0.863916

0.604461

0.984372

0.930999

0.963316

0.817518

1.09509

0.736975

3

2

1.6

166613.2

6.21

8

0.226

0.882121

0.647078

1.17362

0.43104

1.08129

0.903916

1.67451

0.0152

1

1

6.5

19807.47

8.58

0

0.564

0.99772

0.939626

1.42312

0.054376

0.739373

0.354167

1.21041

0.451944

5

4

15.8

38180.87

7.67

0

0.316

0.918505

0.735691

1.44371

0.04363

0.652693

0.231752

1.23616

0.398048

33

18

6.9

7.94

0

0.395

0.923755

0.748809

0.882271

0.53072

0.804437

0.468832

0.840329

0.468654

10

5

16.1

8.83

0

0.26

0.964233

0.852113

0.870627

0.491123

1.16043

0.734412

1.17217

0.539132

1

1

1.2

4.96

0

1.008

0.872209

0.623719

0.695656

0.106426

1.49947

0.202109

1.19864

0.477905

3

2

5.2

51764.25

9.45

0

0.792

1.07945

0.880621

0.991366

0.960458

1.20511

0.643621

1.39024

0.161108

27

16

21.6

84813.92

4.93

0

0.745

0.857205

0.589075

0.950571

0.790652

0.946767

0.777823

1.20637

0.460765

2

2

13.5

24144.33

6.12

0

0.27

0.844123

0.559613

0.828875

0.363099

0.713938

0.314624

0.655945

0.120937

1

1

18.2

7530.29

4.92

0

0.648

1.02882

0.98333

0.993122

0.967866

0.808269

0.476171

0.908654

0.675566

5

4

11.1

50968.05

7.19

0

0.314

0.806266

0.478608

0.989817

0.953929

0.836154

0.531422

0.851673

0.500412

20

13

13.6

95254.46

5.45

8

0.11

0.874445

0.628958

0.936483

0.733844

0.76466

0.396455

0.852855

0.503786

4

4

12.4

50060.15

6.31

0

0.485

0.835755

0.541149

0.860896

0.459287

0.957319

0.803073

1.0087

0.98086

33

12

46.1

31745.47

7.44

0

0.221

0.859304

0.593868

0.837652

0.388122

0.904762

0.67985

0.884598

0.598673

10

4

36.1

10844.46

9.75

0

0.301

0.862507

0.601215

1.01808

0.937039

1.00928

0.929926

1.23251

0.405448

284455.3 40889.73 137886.7

No. of Pages 73

Q71UZ2_RAT

6.1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

GSTM1_RAT

1

NSC 16186

LRC59_RAT

1

22 April 2015

G3V9L3_RAT

Protein Tmem88b OS = Rattus norvegicus GN = Tmem88b PE = 4 SV = 1 Protein Dusp3 OS = Rattus norvegicus GN = Dusp3 PE = 4 SV = 1 Leucine-rich repeat-containing protein 59 OS = Rattus norvegicus GN = Lrrc59 PE = 1 SV = 1 Protein Ganab OS = Rattus norvegicus GN = Ganab PE = 2 SV = 1 Glyceraldehyde-3-phosphate dehydrogenase OS = Rattus norvegicus GN = Gapdh PE = 1 SV = 3 Cytosolic non-specific dipeptidase OS = Rattus norvegicus GN = Cndp2 PE = 1 SV = 1 Protein Tubb6 OS = Rattus norvegicus GN = Tubb6 PE = 2 SV = 1 Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform OS = Rattus norvegicus GN = Ppp3cb PE = 2 SV = 1 Cation-dependent mannose-6-phosphate receptor OS = Rattus norvegicus GN = M6pr PE = 2 SV = 1 14-3-3 protein epsilon OS = Rattus norvegicus GN = Ywhae PE = 1 SV = 1 Glutathione S-transferase Mu 1 OS = Rattus norvegicus GN = Gstm1 PE = 2 SV = 1 Cyp46a1 protein OS = Rattus norvegicus GN = Cyp46a1 PE = 2 SV = 1 Glucose-6-phosphate isomerase OS = Rattus norvegicus GN = Gpi PE = 1 SV = 1 Ubiquitin carboxyl-terminal hydrolase OS = Rattus norvegicus GN = Usp5 PE = 3 SV = 1 Succinate-semialdehyde dehydrogenase, mitochondrial OS = Rattus norvegicus GN = Aldh5a1 PE = 1 SV = 2 Latrophilin-1 OS = Rattus norvegicus GN = Lphn1 PE = 1 SV = 1 Protein Snx12 OS = Rattus norvegicus GN = Snx12 PE = 2 SV = 1 Uncharacterized protein (Fragment) OS = Rattus norvegicus PE = 2 SV = 1 270 kDa ankyrin G isoform (Fragment) OS = Rattus norvegicus GN = Ank3 PE = 2 SV = 2 Pdhx protein (Fragment) OS = Rattus norvegicus GN = Pdhx PE = 2 SV = 1 STE20-like serine/threonine-protein kinase OS = Rattus norvegicus GN = Slk PE = 1 SV = 1 NADH-ubiquinone oxidoreductase chain 4 OS = Rattus norvegicus GN = Mt-nd4 PE = 2 SV = 1 Heat shock protein HSP 90-alpha OS = Rattus norvegicus GN = Hsp90aa1 PE = 1 SV = 3 Sodium channel subunit beta-2 OS = Rattus norvegicus GN = Scn2b PE = 1 SV = 1 Regulator of G-protein signaling 6 (Fragment) OS = Rattus norvegicus GN = Rgs6 PE = 2 SV = 1 LanC lantibiotic synthetase component C-like 2 (Bacterial) OS = Rattus norvegicus GN = Lancl2 PE = 2 SV = 1 Sarco/endoplasmic reticulum Ca2+-ATPase (Fragment) OS = Rattus norvegicus GN = Atp2a2 PE = 2 SV = 1 Elongation factor 1-gamma OS = Rattus norvegicus GN = Eef1g PE = 1 SV = 3 Voltage-dependent anion-selective channel protein 2 OS = Rattus norvegicus GN = Vdac2 PE = 1 SV = 2 NADH dehydrogenase (Ubiquinone) 1 alpha subcomplex, 2 (Predicted) OS = Rattus norvegicus GN = Ndufa2 PE = 4

48

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

D4AAB3_RAT

NDRG1_RAT D3ZXQ2_RAT B6DYP8_RAT ATP5J_RAT SNAA_RAT NRX2A_RAT CSKP_RAT D3ZWC6_RAT G3V7Q6_RAT D3ZEG8_RAT F1M4V6_RAT Q5XI77_RAT F1M779_RAT B4F762_RAT GTDC2_RAT D3ZDH8_RAT GLNA_RAT B0K026_RAT PRRT2_RAT B2GV57_RAT Q6AXY8_RAT APEX1_RAT D3ZUF9_RAT

F1LZW6_RAT MSRB2_RAT

12.0

95706.91

4.77

0

1.124

0.805278

0.476583

0.790954

0.266933

0.993045

0.88995

0.962815

0.860423

5

4

6.6

82663.94

9.16

0

0.081

0.868067

0.614068

1.167

0.448882

0.689674

0.279717

1.1802

0.520168

16

7

11.1

82660.35

5.38

12

0.022

0.903279

0.698097

0.80491

0.300062

0.928558

0.73481

0.93576

0.766418

3

1

4.1

42954.21

5.77

0

0.303

0.779252

0.424968

0.752624

0.189184

0.888112

0.642362

0.963695

0.86352

1

1

1.2

9.09

0

0.528

0.979463

0.891755

0.831369

0.370105

1.2863

0.492165

1.34075

0.221446

3

2

10.4

25319.09

8.78

0

0.324

1.05248

0.9352

1.05274

0.812772

0.994403

0.893283

1.16561

0.554896

14

4

22.2

12494.27

9.43

0

0.546

0.932151

0.769933

0.796538

0.279875

0.730919

0.340688

0.7115

0.192943

16

10

40.7

33192.31

5.3

0

0.355

0.865905

0.609057

1.04853

0.827656

0.833459

0.525945

0.999496

0.990843

2

2

1.4

184299.3

5.63

0

0.369

0.919972

0.739349

0.824993

0.352362

1.14371

0.769458

1.19772

0.479975

5

5

7.1

102112.4

5.93

0

0.405

0.83954

0.549464

0.775771

0.23385

0.974652

0.844989

0.759958

0.278013

1

1

1.7

58291.77

8.51

0

0.268

0.83434

0.538059

1.05542

0.803299

1.05297

0.966106

1.26647

0.339813

2

2

10.7

28559.08

6.52

0

0.114

0.892503

0.671924

0.902597

0.603522

0.900534

0.670251

0.982938

0.931729

137023.7

8.23

0

0.214

0.831855

0.532649

0.961151

0.834077

1.13545

0.786953

1.24627

0.377975

5.68

0

0.55

0.886497

0.657505

1.03781

0.865917

0.979594

0.857025

1.10041

0.722558

7.53

0

0.511

0.800224

0.466298

0.846617

0.414738

0.860885

0.583008

0.900894

0.65034

5.48

0

0.241

0.888028

0.66117

1.0846

0.702467

0.869726

0.602001

1.20264

0.469002

63619.06

5.71

0

0.016

0.736847

0.348248

1.18243

0.407925

0.772548

0.410246

1.43124

0.121295

2.9

66716.35

8.74

0

0.11

0.880691

0.643686

0.828466

0.361958

0.702262

0.297484

0.908293

0.674386

11

28.3

43891.81

6.21

0

0.584

0.857791

0.59041

0.882519

0.531582

0.996179

0.89765

1.08948

0.752298

20

12

33.2

42267.34

6.64

0

0.595

0.859685

0.59474

0.748973

0.182757

0.924357

0.725

0.845255

0.482306

3

2

6.2

43120.76

10.68

0

0.351

0.703739

0.294904

1.04509

0.839915

0.873291

0.609737

1.28929

0.299774

2

2

7.0

35820.21

4.58

0

0.588

0.930636

0.76611

0.766507

0.215151

1.04292

0.988233

0.86923

0.551729

1

1

6.7

29107.09

9.05

0

0.1

0.955979

0.830779

1.00633

0.979684

0.704138

0.300195

0.907959

0.673293

1

1

3.2

34014.88

8.5

0

0.969438

0.865626

0.844886

0.409517

1.10679

0.84841

1.15159

0.589327

1

1

4.7

35538.05

8.04

0

0.59

0.778091

0.422743

0.754884

0.193247

0.682285

0.269631

0.612127

0.080604

2

2

2.3

113059.6

6.67

0

0.456

0.865217

0.607466

1.07988

0.718485

1.01081

0.933723

1.43872

0.114938

6

3

3.5

113659.1

5.16

0

0.395

0.799079

0.463987

0.751428

0.187061

0.842557

0.544554

0.804866

0.376928

5

4

7.7

74381.91

8.86

0

0.022

0.853661

0.581022

0.930538

0.710281

1.01184

0.936249

1.22518

0.42054

1

1

11.5

19072.69

9.19

0

0.532

0.828817

0.526077

0.880794

0.52561

1.06154

0.947245

1.10125

0.720284

3

2

12.4

3

3

2.0

2

2

5.4

57

34

24.7

1

1

1.3

1

1

20

29872.79 186960.6 54159.87 191557.4

0.025

(continued on next page)

49

No. of Pages 73

CA2D1_RAT

9

NSC 16186

SV2A_RAT

15

22 April 2015

ECHA_RAT

SV = 1 Neurofilament 3, medium OS = Rattus norvegicus GN = Nefm PE = 3 SV = 1 Trifunctional enzyme subunit alpha, mitochondrial OS = Rattus norvegicus GN = Hadha PE = 1 SV = 2 Synaptic vesicle glycoprotein 2A OS = Rattus norvegicus GN = Sv2a PE = 1 SV = 2 Protein NDRG1 OS = Rattus norvegicus GN = Ndrg1 PE = 1 SV = 1 Uncharacterized protein OS = Rattus norvegicus PE = 4 SV = 1 Glutathione S-transferase OS = Rattus norvegicus GN = Gsta1 PE = 2 SV = 1 ATP synthase-coupling factor 6, mitochondrial OS = Rattus norvegicus GN = Atp5j PE = 1 SV = 1 Alpha-soluble NSF attachment protein OS = Rattus norvegicus GN = Napa PE = 1 SV = 2 Isoform 4a of Neurexin-2 OS = Rattus norvegicus GN = Nrxn2 Peripheral plasma membrane protein CASK OS = Rattus norvegicus GN = Cask PE = 2 SV = 1 Protein Sntb1 OS = Rattus norvegicus GN = Sntb1 PE = 4 SV = 1 Proteasome subunit beta type OS = Rattus norvegicus GN = Psmb5 PE = 3 SV = 1 Protein RGD1309188 OS = Rattus norvegicus GN = RGD1309188 PE = 4 SV = 1 Kalirin (Fragment) OS = Rattus norvegicus GN = Kalrn PE = 2 SV = 1 Annexin OS = Rattus norvegicus GN = Anxa11 PE = 2 SV = 1 Clathrin heavy chain 1 OS = Rattus norvegicus GN = Cltc PE = 2 SV = 1 Fanconi anemia group C protein homolog OS = Rattus norvegicus GN = Fancc PE = 2 SV = 1 Glycosyltransferase-like domain-containing protein 2 OS = Rattus norvegicus GN = Gtdc2 PE = 2 SV = 1 Platelet glycoprotein Ib beta chain OS = Rattus norvegicus GN = Gp1bb PE = 3 SV = 1 Glutamine synthetase OS = Rattus norvegicus GN = Glul PE = 1 SV = 3 Letmd1 protein OS = Rattus norvegicus GN = Letmd1 PE = 2 SV = 1 Proline-rich transmembrane protein 2 OS = Rattus norvegicus GN = Prrt2 PE = 1 SV = 1 Protein Cars2 OS = Rattus norvegicus GN = Cars2 PE = 2 SV = 1 Dehydrogenase/reductase (SDR family) member 1 OS = Rattus norvegicus GN = Dhrs1 PE = 2 SV = 1 DNA-(apurinic or apyrimidinic site) lyase OS = Rattus norvegicus GN = Apex1 PE = 1 SV = 2 Protein Pitrm1 OS = Rattus norvegicus GN = Pitrm1 PE = 2 SV = 1 Voltage-dependent calcium channel subunit alpha-2/delta-1 OS = Rattus norvegicus GN = Cacna2d1 PE = 2 SV = 1 Protein Slc25a13 (Fragment) OS = Rattus norvegicus GN = Slc25a13 PE = 3 SV = 1 Methionine-R-sulfoxide reductase B2, mitochondrial OS = Rattus norvegicus GN = Msrb2 PE = 2 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

G3V7S2_RAT

DNJA2_RAT G3V985_RAT COR1A_RAT G3V980_RAT YIPF5_RAT F1M5N4_RAT D3ZX82_RAT

GSTK1_RAT NDUA9_RAT

D3Z955_RAT F1LV42_RAT KPCA_RAT Q5D009_RAT RINI_RAT Q7TMZ5_RAT Q5FVT5_RAT GBRL2_RAT D3ZJD3_RAT NPM_RAT AATC_RAT Q6V9V9_RAT Q4V8H5_RAT

SFXN3_RAT CAP2_RAT D3ZQ02_RAT

84870.3

7.08

0

0.427

0.744788

0.361902

0.996766

0.983246

1.15692

0.741713

1.13462

0.632246

2

2

0.9

307688.2

5.84

0

0.337

0.841711

0.55426

0.936889

0.735461

0.900161

0.669407

0.904732

0.662769

1

1

7.3

24358.68

5.84

0

0.046

0.806515

0.479118

0.967852

0.861854

0.601056

0.175005

0.726558

0.217034

3

2

5.6

45765.11

6.06

0

0.695

0.416241

0.045752

0.830187

0.366774

0.570725

0.14691

0.511518

0.027949

4

3

10.2

31768.24

8.89

0

0.454

0.895435

0.679008

0.902831

0.604386

1.01702

0.949069

1.18959

0.498397

2

2

5.9

51064.7

6.05

0

0.275

0.854836

0.583687

0.832143

0.372297

0.916122

0.705897

0.882423

0.591921

4

2

14.8

20642.26

4.73

0

0.178

0.745498

0.363139

0.815324

0.326501

0.989351

0.880885

0.889403

0.613713

1

1

3.5

27902.84

4.2

1

0.379

0.841216

0.553164

1.31579

0.151302

0.89431

0.656216

1.34633

0.213934

15

8

16.3

60834.62

6.05

0

0.13

0.772203

0.411572

1.15331

0.487113

1.10368

0.855165

1.55027

0.047809

9

4

5.3

8.21

0

0.162

0.851219

0.575504

1.0336

0.881013

0.956236

0.800473

0.973433

0.897942

2

2

8.5

28574.47

6.23

0

0.266

0.828151

0.524641

1.17607

0.424518

1.43813

0.268652

1.80709

0.003659

2

1

7.1

25492.69

9.13

0

0.116

0.955722

0.830117

1.1858

0.399285

0.574814

0.150482

0.995738

0.977409

14

8

18.6

42558.67

9.83

0

0.091

0.828403

0.525183

0.980784

0.915917

0.88844

0.64309

1.13327

0.635714

3

3

5.5

70233.66

6.09

0

0.301

1.14163

0.757366

1.40012

0.068903

0.696466

0.289212

1.04028

0.890249

11

8

4.1

8.8

0

0.562

0.835565

0.540733

1.07199

0.745533

0.881462

0.627632

0.98406

0.935726

5

5

9.8

76791.12

6.61

0

0.479

0.794451

0.454705

0.865322

0.47362

0.811159

0.481747

0.863868

0.535786

1

1

4.2

29761.16

8.97

4

0.189

0.666022

0.241162

0.929742

0.707147

0.893427

0.654236

0.909609

0.678699

1

1

3.3

49973.97

4.67

0

0.024

0.674509

0.252608

0.972778

0.882385

0.676231

0.261555

0.7293

0.221644

1

1

4.9

23450.65

9.38

0

0.204

0.83998

0.550433

1.04517

0.839619

0.847967

0.555773

1.03502

0.905282

2

2

5.1

49094.48

8.09

0

0.326

0.687385

0.270689

1.10161

0.645914

0.954909

0.797287

1.22266

0.425805

2

2

17.1

13666.68

7.81

0

0.316

0.827794

0.523872

0.798912

0.285502

0.959027

0.80718

0.852172

0.501837

2

2

10.2

15720.34

11.92

0

0.693

0.909015

0.712178

0.909517

0.629294

0.936264

0.752921

0.975125

0.903945

1

1

4.9

29524.38

4.45

0

0.912

0.784956

0.435992

0.6458

0.06034

0.724433

0.330575

0.573258

0.054687

10

6

17.0

46428.17

6.73

0

0.305

0.819838

0.506891

0.929055

0.704446

1.15163

0.752784

1.6187

0.026007

2

2

5.6

48157.16

6.33

0

0.538

0.940587

0.791334

0.947439

0.777913

1.32843

0.421847

1.48648

0.080327

2

2

5.3

52554.63

6.82

0

0.152

0.923218

0.747463

1.12006

0.586794

0.913707

0.700331

1.03436

0.907174

1

1

7.4

33699.54

4.3

0

0.663

1.03598

0.968752

1.03798

0.865293

0.808302

0.476234

1.01798

0.954168

5

3

13.9

31668.71

9.71

0

0.119

0.775033

0.41692

0.756175

0.195595

0.853744

0.567876

0.788121

0.337758

5

4

13.4

52911.71

6.69

0

0.413

0.771448

0.410151

0.925287

0.689699

0.989481

0.881206

1.07391

0.795343

1

1

2.0

48891.51

6.67

0

0.373

0.934544

0.775987

0.934294

0.725137

0.773351

0.411665

0.927042

0.736776

111789.1

215355.6

No. of Pages 73

Q9Z1X8_RAT

6.6

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

ERP29_RAT

3

NSC 16186

TPPC4_RAT

4

22 April 2015

F1LX73_RAT

Protein Adam11 OS = Rattus norvegicus GN = Adam11 PE = 2 SV = 1 Protein Nbea OS = Rattus norvegicus GN = Nbea PE = 4 SV = 1 Trafficking protein particle complex subunit 4 OS = Rattus norvegicus GN = Trappc4 PE = 2 SV = 1 DnaJ homolog subfamily A member 2 OS = Rattus norvegicus GN = Dnaja2 PE = 2 SV = 1 Protein Sco1 OS = Rattus norvegicus GN = Sco1 PE = 4 SV = 1 Coronin-1A OS = Rattus norvegicus GN = Coro1a PE = 1 SV = 3 Protein Rap2a OS = Rattus norvegicus GN = Rap2a PE = 4 SV = 1 Protein YIPF5 OS = Rattus norvegicus GN = Yipf5 PE = 2 SV = 1 Malic enzyme (Fragment) OS = Rattus norvegicus GN = Me3 PE = 2 SV = 1 Protein Cyfip2 OS = Rattus norvegicus GN = Cyfip2 PE = 2 SV = 1 Endoplasmic reticulum resident protein 29 OS = Rattus norvegicus GN = Erp29 PE = 1 SV = 2 Glutathione S-transferase kappa 1 OS = Rattus norvegicus GN = Gstk1 PE = 1 SV = 3 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial OS = Rattus norvegicus GN = Ndufa9 PE = 1 SV = 2 Protein Pgm2l1 OS = Rattus norvegicus GN = Pgm2l1 PE = 4 SV = 1 Uncharacterized protein (Fragment) OS = Rattus norvegicus PE = 2 SV = 1 Protein kinase C alpha type OS = Rattus norvegicus GN = Prkca PE = 1 SV = 3 Scamp1 protein (Fragment) OS = Rattus norvegicus GN = Scamp1 PE = 2 SV = 1 Ribonuclease inhibitor OS = Rattus norvegicus GN = Rnh1 PE = 1 SV = 2 ADP-ribosylation factor-like 6 interacting protein 1 OS = Rattus norvegicus GN = Arl6ip1 PE = 2 SV = 1 Pyruvate dehydrogenase kinase, isozyme 1 OS = Rattus norvegicus GN = Pdk1 PE = 2 SV = 1 Gamma-aminobutyric acid receptor-associated protein-like 2 OS = Rattus norvegicus GN = Gabarapl2 PE = 3 SV = 1 Protein RGD1565183 OS = Rattus norvegicus GN = RGD1565183 PE = 4 SV = 1 Nucleophosmin OS = Rattus norvegicus GN = Npm1 PE = 2 SV = 1 Aspartate aminotransferase, cytoplasmic OS = Rattus norvegicus GN = Got1 PE = 1 SV = 3 Protein Stk25 OS = Rattus norvegicus GN = Stk25 PE = 2 SV = 1 Aspartyl aminopeptidase OS = Rattus norvegicus GN = Dnpep PE = 2 SV = 1 Neural F box protein NFB42 OS = Rattus norvegicus GN = Fbxo2 PE = 2 SV = 1 Sideroflexin-3 OS = Rattus norvegicus GN = Sfxn3 PE = 2 SV = 1 Adenylyl cyclase-associated protein 2 OS = Rattus norvegicus GN = Cap2 PE = 2 SV = 1 Protein Wdr37 OS = Rattus norvegicus GN = Wdr37 PE = 2 SV = 1

50

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

D4A6U1_RAT

D3ZJR1_RAT GBRB2_RAT GBRB3_RAT A4_RAT D3ZAI6_RAT A1L1L9_RAT D4ADW6_RAT DLDH_RAT RAB35_RAT G3V6P7_RAT Q6P9Y4_RAT G3V6H9_RAT Q3B8N9_RAT B2RYN6_RAT HBA_RAT MDHM_RAT D4A0F5_RAT B0BN30_RAT D4A5W8_RAT Q5RKG9_RAT MPPA_RAT Q68FU2_RAT WDR1_RAT

MSRA_RAT NDUS1_RAT

0.492

0.779674

0.425777

0.909023

0.627438

0.971429

0.837156

1.02647

0.929787

6.29

0

0.198

0.816146

0.499113

0.971785

0.878242

1.02189

0.961128

1.41425

0.136747

68163.27

7.33

0

0.31

0.791299

0.448443

1.01331

0.954328

1.05198

0.968266

1.10437

0.711859

1.2

99113.2

4.88

0

0.119

0.963653

0.850611

1.05714

0.797248

1.00539

0.920346

1.18342

0.51265

3

7.8

54632.84

9.35

4

0.068

0.989524

0.9181

0.563934

0.020803

0.572114

0.148116

0.483

0.02003

5

4

11.6

54165.03

9.19

4

0.09

1.01713

0.990749

0.83447

0.37893

0.617133

0.191436

0.71093

0.192071

3

3

4.2

86703.2

4.73

1

0.546

0.865215

0.607461

1.1416

0.52114

0.927828

0.733103

1.11944

0.671734

6

4

8.4

63123.72

8.74

0

0.358

0.805198

0.476419

1.001

0.999048

0.821114

0.501224

1.0385

0.895337

7

3

16.8

24662.53

6.96

0

0.119

0.792677

0.451174

1.18341

0.405393

0.83694

0.533026

0.994449

0.972805

1

1

1.1

5.87

0

0.845

1.06509

0.909628

1.42773

0.051797

0.822411

0.503792

1.06638

0.816367

17

11

20.6

54037.46

7.96

0

0.01

0.814606

0.495885

0.854523

0.43908

0.722889

0.328196

0.955637

0.835227

8

4

23.9

23024.96

8.53

0

0.473

0.865972

0.60921

0.983205

0.92609

1.51847

0.184171

1.35665

0.200511

7

6

3.8

5.54

0

0.84

0.797651

0.46111

0.946062

0.772333

0.760278

0.388915

0.793343

0.349682

71

15

32.2

32903.92

9.76

4

0.056

0.804763

0.475529

0.908046

0.623776

0.983997

0.867778

1.0321

0.913627

3

1

2.6

45372.63

4.36

0

0.956

0.793195

0.452202

0.926743

0.695381

0.797763

0.456201

0.870652

0.555995

5

3

16.2

32822.46

8.94

0

0.258

1.08364

0.8722

1.23357

0.288923

0.655522

0.235201

1.22044

0.430477

1

1

1.2

91720.87

6.36

0

0.126

0.877326

0.635733

0.983698

0.928164

0.871541

0.605933

1.01571

0.9607

79

10

60.6

15328.35

7.81

0

0.115

0.834101

0.537536

1.68349

0.001873

0.861644

0.584628

2.13924

4.04E05

108

19

57.7

35683.15

8.93

0

0.119

0.802726

0.471373

1.13907

0.528651

1.02813

0.976591

1.48366

0.082107

21

9

23.5

48627.19

8.76

0

0.783

0.828419

0.525219

0.938329

0.741213

0.992621

0.888908

1.07672

0.787515

7

3

9.8

41591.89

9.4

2

0.094

0.913734

0.723837

0.935914

0.731578

0.987568

0.876517

1.06938

0.80799

2

2

4.3

62469.26

9

0

0.123

0.795486

0.456771

0.976368

0.897398

0.878206

0.620473

0.977486

0.912332

2

1

1.6

69063.29

5.59

0

1.585

0.684792

0.266978

0.735568

0.160541

1.15615

0.743337

1.04218

0.88484

1

1

2.1

58606.91

8.29

0

0.193

0.975558

0.881561

0.892259

0.565933

0.864368

0.590457

1.12618

0.654086

3

3

10.8

40626.38

7.57

0

0.001

0.807695

0.481545

0.889388

0.555699

0.769396

0.4047

1.00551

0.990043

9

7

11.6

66180.66

6.15

0

0.265

0.789091

0.444086

0.86413

0.469737

1.28971

0.486246

1.37491

0.178303

3

2

11.2

17123.59

6.13

0

0.272

0.774612

0.416122

0.772653

0.227432

1.33986

0.403838

1.25909

0.353463

1

1

4.7

25850.95

8.21

0

0.454

0.880597

0.643464

1.01688

0.941368

0.830325

0.51961

1.03186

0.914325

40

17

27.9

79411.47

5.65

0

0.101

0.823606

0.514898

1.09733

0.659978

0.876583

0.616919

1.08311

0.769824

16.2

72

27

27.9

7

7

16.2

1

1

3

40597.33 102406.9

145586.8

226410.6

51

(continued on next page)

No. of Pages 73

UBE2N_RAT

0

6

NSC 16186

Q66HF3_RAT

6.74

13

22 April 2015

HXK1_RAT

Neuronal-specific septin-3 OS = Rattus norvegicus GN = Sept3 PE = 1 SV = 2 Hexokinase-1 OS = Rattus norvegicus GN = Hk1 PE = 1 SV = 4 Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial OS = Rattus norvegicus GN = Etfdh PE = 2 SV = 1 Protein Eps15l1 (Fragment) OS = Rattus norvegicus GN = Eps15l1 PE = 2 SV = 1 Gamma-aminobutyric acid receptor subunit beta-2 OS = Rattus norvegicus GN = Gabrb2 PE = 1 SV = 1 Gamma-aminobutyric acid receptor subunit beta-3 OS = Rattus norvegicus GN = Gabrb3 PE = 1 SV = 1 Amyloid beta A4 protein OS = Rattus norvegicus GN = App PE = 1 SV = 2 Protein Nt5dc3 OS = Rattus norvegicus GN = Nt5dc3 PE = 3 SV = 1 Protein RGD1563224 OS = Rattus norvegicus GN = RGD1563224 PE = 2 SV = 1 Protein Ktn1 OS = Rattus norvegicus GN = Ktn1 PE = 2 SV = 1 Dihydrolipoyl dehydrogenase, mitochondrial OS = Rattus norvegicus GN = Dld PE = 1 SV = 1 Ras-related protein Rab-35 OS = Rattus norvegicus GN = Rab35 PE = 2 SV = 1 Myosin, heavy polypeptide 9, non-muscle OS = Rattus norvegicus GN = Myh9 PE = 4 SV = 1 ADP/ATP translocase 1 OS = Rattus norvegicus GN = Slc25a4 PE = 2 SV = 1 Nucleosome assembly protein 1-like 1 OS = Rattus norvegicus GN = Nap1l1 PE = 3 SV = 1 Biphenyl hydrolase-like (Serine hydrolase) OS = Rattus norvegicus GN = Bphl PE = 2 SV = 1 Protein Ap1g1 OS = Rattus norvegicus GN = Ap1g1 PE = 2 SV = 1 Hemoglobin subunit alpha-1/2 OS = Rattus norvegicus GN = Hba1 PE = 1 SV = 3 Malate dehydrogenase, mitochondrial OS = Rattus norvegicus GN = Mdh2 PE = 1 SV = 2 Septin-7 OS = Rattus norvegicus GN = Sept7 PE = 2 SV = 1 Mtch1 protein OS = Rattus norvegicus GN = Mtch1 PE = 2 SV = 1 Protein Pgs1 OS = Rattus norvegicus GN = Pgs1 PE = 4 SV = 1 Eukaryotic translation initiation factor 4B OS = Rattus norvegicus GN = Eif4b PE = 2 SV = 1 Mitochondrial-processing peptidase subunit alpha OS = Rattus norvegicus GN = Pmpca PE = 1 SV = 1 Phosphoserine aminotransferase 1 OS = Rattus norvegicus GN = Psat1 PE = 2 SV = 1 WD repeat-containing protein 1 OS = Rattus norvegicus GN = Wdr1 PE = 1 SV = 3 Ubiquitin-conjugating enzyme E2 N OS = Rattus norvegicus GN = Ube2n PE = 1 SV = 1 Mitochondrial peptide methionine sulfoxide reductase OS = Rattus norvegicus GN = Msra PE = 1 SV = 1 NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial OS = Rattus norvegicus GN = Ndufs1 PE = 1 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

SEPT3_RAT

AL1B1_RAT B5DFN2_RAT ARP3_RAT MRCKB_RAT D3ZXT1_RAT MTOR_RAT NMDZ1_RAT

AT5F1_RAT WDR7_RAT PTPRS_RAT GELS_RAT COMT_RAT AK1A1_RAT KAD3_RAT SYVC_RAT PDK2_RAT

ABHGA_RAT Q6P7S6_RAT ECHB_RAT GUAA_RAT ARBK1_RAT GPX1_RAT APOD_RAT

D4A746_RAT

THIO_RAT

16776.35

9.47

0

0.437

0.733854

0.343188

0.808524

0.309072

0.764159

0.395588

0.840991

0.470477

10

5

28.4

24673.75

8.96

0

0.422

0.761792

0.392252

1.14061

0.524055

1.1162

0.828118

1.92243

0.000892

5

3

8.7

25617.25

6.13

0

0.398

0.832062

0.533099

0.949513

0.786343

0.883791

0.632774

1.03968

0.891967

12

6

17.9

57624.14

6.62

0

0.248

0.907063

0.707376

1.11556

0.600973

0.825432

0.5098

1.11127

0.693398

6

5

11.3

58908.89

7.02

0

0.26

0.743862

0.360293

0.818653

0.335262

0.818767

0.496593

0.838365

0.463273

8

3

9.6

47356.6

5.61

0

0.267

0.805655

0.477354

1.06384

0.773799

1.11312

0.834755

1.19369

0.489057

1

1

0.9

194885.5

6.05

0

0.572

0.914535

0.725824

0.77776

0.23801

0.864647

0.591055

0.870746

0.556277

1

1

1.4

6.7

0

0.116

0.634438

0.201786

1.04212

0.850494

0.975642

0.847396

1.14137

0.615016

2

2

0.6

288791.2

6.73

0

0.191

0.835607

0.540825

1.19482

0.376702

0.971526

0.837393

1.23802

0.394308

3

2

3.2

105507.7

8.99

3

0.27

0.758585

0.386411

0.81388

0.322748

0.997543

0.901003

1.08062

0.776717

1

1

5.7

14865.28

10.51

0

0.194

0.840155

0.550819

0.809539

0.311633

1.12629

0.806477

1.07177

0.801286

23

8

23.8

28868.45

9.39

0

0.137

0.760896

0.390614

1.0999

0.651526

0.834683

0.528428

1.53762

0.053187

71990.93

6

3

2.5

160191.7

6.57

0

0.091

0.911093

0.717305

1.44879

0.041275

0.637335

0.213657

0.984874

0.938627

6

4

4.1

207076.1

6.92

0

0.351

0.819094

0.505319

0.879878

0.522452

0.674546

0.259337

0.862672

0.532262

5 3

3 2

4.5 15.8

86285.01 24747.16

5.9 5.11

0 0

0.454 0.241

0.788199 0.830074

0.442333 0.52879

0.906926 0.973229

0.619591 0.884268

0.748352 0.746963

0.368844 0.366549

0.865175 1.09579

0.539652 0.735066

4

4

17.9

36505.43

6.84

0

0.289

0.620723

0.18623

0.777546

0.23756

0.949965

0.785452

1.07346

0.796585

1

1

4.4

25438.03

8.89

0

0.327

0.701577

0.291623

1.07895

0.721659

0.960926

0.811753

1.0367

0.900472

4

3

3.2

7.54

0

0.305

0.941755

0.794311

0.681334

0.090979

0.75328

0.377059

0.985897

0.942273

5

3

10.3

46105.15

6.13

0

0.256

0.861107

0.597998

1.00456

0.986106

0.883345

0.631787

1.06168

0.82958

4

4

8.8

63037.39

8.5

2

0.191

1.20439

0.638928

0.982588

0.923496

0.887397

0.64077

1.43789

0.115635

1 6

1 4

2.2 8.0

51463.85 51413.9

5.53 9.5

0 0

0.54 0.073

0.754831 0.823365

0.379646 0.514383

1.15908 1.063

0.47078 0.776704

1.11136 0.866445

0.83855 0.594919

1.30806 1.01988

0.2693 0.948711

1

1

1.6

76756.55

6.21

0

0.175

0.869687

0.617834

1.31422

0.153344

0.770382

0.406431

1.24941

0.371886

1

1

2.3

79783.92

6.54

0

0.464

0.745675

0.363448

1.18409

0.403657

0.874434

0.612226

1.33825

0.224879

1

1

6.0

22154.99

7.7

0

0.315

0.893576

0.674514

1.42816

0.05156

0.802977

0.466051

1.5525

0.046909

1

1

8.5

21634.61

4.93

0

0.138

0.876015

0.632645

1.03064

0.891662

0.619456

0.193901

0.827132

0.433155

3

2

7.6

29717.85

5.23

0

0.167

0.806716

0.479531

0.959815

0.828565

1.14371

0.769456

1.265

0.3425

1

1

2.2

39902.06

6.27

0

0.056

0.803562

0.473076

1.00159

0.996891

0.973259

0.841603

1.22274

0.425642

3

3

31.4

11673.36

4.8

0

0.006

0.826394

0.520864

0.865009

0.472599

1.04019

0.994243

0.996079

0.978628

140366.7

No. of Pages 73

Q5U1Z9_RAT

47.2

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

RL23_RAT

9

NSC 16186

G3V8H3_RAT

15

22 April 2015

SODM_RAT

RCG38845, isoform CRA_b OS = Rattus norvegicus GN = LOC100911483 PE = 4 SV = 1 Superoxide dismutase [Mn], mitochondrial OS = Rattus norvegicus GN = Sod2 PE = 1 SV = 2 Glutathione S-transferase Yb-3 OS = Rattus norvegicus GN = Gstm3 PE = 3 SV = 1 Aldehyde dehydrogenase X, mitochondrial OS = Rattus norvegicus GN = Aldh1b1 PE = 1 SV = 1 Adenosylhomocysteinase OS = Rattus norvegicus GN = Ahcyl1 PE = 2 SV = 1 Actin-related protein 3 OS = Rattus norvegicus GN = Actr3 PE = 1 SV = 1 Serine/threonine-protein kinase MRCK beta OS = Rattus norvegicus GN = Cdc42bpb PE = 1 SV = 1 Leucine rich repeat containing 4C (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Lrrc4c PE = 4 SV = 1 Serine/threonine-protein kinase mTOR OS = Rattus norvegicus GN = Mtor PE = 1 SV = 1 Glutamate receptor ionotropic, NMDA 1 OS = Rattus norvegicus GN = Grin1 PE = 1 SV = 1 60S ribosomal protein L23 OS = Rattus norvegicus GN = Rpl23 PE = 2 SV = 1 ATP synthase subunit b, mitochondrial OS = Rattus norvegicus GN = Atp5f1 PE = 1 SV = 1 Isoform 2 of WD repeat-containing protein 7 OS = Rattus norvegicus GN = Wdr7 Isoform 2 of Receptor-type tyrosine-protein phosphatase S OS = Rattus norvegicus GN = Ptprs Gelsolin OS = Rattus norvegicus GN = Gsn PE = 4 SV = 1 Isoform 2 of Catechol O-methyltransferase OS = Rattus norvegicus GN = Comt Alcohol dehydrogenase [NADP(+)] OS = Rattus norvegicus GN = Akr1a1 PE = 1 SV = 2 GTP:AMP phosphotransferase, mitochondrial OS = Rattus norvegicus GN = Ak3 PE = 2 SV = 2 Valine–tRNA ligase OS = Rattus norvegicus GN = Vars PE = 2 SV = 2 [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial OS = Rattus norvegicus GN = Pdk2 PE = 1 SV = 1 Abhydrolase domain-containing protein 16A OS = Rattus norvegicus GN = Abhd16a PE = 2 SV = 1 Clusterin OS = Rattus norvegicus GN = Clu PE = 2 SV = 1 Trifunctional enzyme subunit beta, mitochondrial OS = Rattus norvegicus GN = Hadhb PE = 1 SV = 1 GMP synthase [glutamine-hydrolyzing] OS = Rattus norvegicus GN = Gmps PE = 1 SV = 1 Beta-adrenergic receptor kinase 1 OS = Rattus norvegicus GN = Adrbk1 PE = 2 SV = 1 Glutathione peroxidase 1 OS = Rattus norvegicus GN = Gpx1 PE = 1 SV = 4 Apolipoprotein D OS = Rattus norvegicus GN = Apod PE = 1 SV = 1 Metaxin 2 OS = Rattus norvegicus GN = Mtx2 PE = 2 SV = 1 GDP-mannose pyrophosphorylase B (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Gmppb PE = 4 SV = 1 Thioredoxin OS = Rattus norvegicus GN = Txn PE = 1 SV = 2

52

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

D3ZE15_RAT

KAP3_RAT

PRDX5_RAT IP3KA_RAT D3ZWA8_RAT B2RZ72_RAT

Q3MHS9_RAT BACH_RAT AMPL_RAT ABCB7_RAT F1M6P0_RAT G3V9U2_RAT A1AT_RAT RAB18_RAT VAPA_RAT GDIR1_RAT LASP1_RAT RNF34_RAT D3ZRT6_RAT B0BMV5_RAT FAHD2_RAT GTPB1_RAT VPS45_RAT LAC2_RAT

GRM2_RAT GPDM_RAT D3ZRJ0_RAT

18.3

67719.85

8.03

0

0.231

0.777928

0.422431

1.05197

0.81549

0.815307

0.489811

1.18936

0.498931

12

6

30.1

28172.23

9.11

0

0.067

0.832342

0.533708

1.06995

0.752569

0.789935

0.441632

1.10933

0.698563

7

5

13.0

35587.88

9.22

2

0.016

0.855036

0.58414

0.887629

0.549472

0.688645

0.278297

1.08739

0.758045

9

6

21.9

46122.44

4.9

0

0.792076

0.449982

0.780507

0.243842

0.750603

0.372582

0.79566

0.355059

15

9

45.5

22178.44

8.94

0

0.179

0.869

0.616237

1.40329

0.066725

0.84489

0.549379

1.49855

0.073074

5

3

8.7

50870.04

7.65

0

0.543

0.799794

0.46543

0.818549

0.334984

1.37554

0.350659

1.16817

0.548718

2

2

3.1

79363.19

5.24

0

0.579

0.799953

0.46575

1.05426

0.807404

0.655469

0.235137

0.82959

0.439647

3

3

17.3

19666.8

8.53

0

0.133

0.740665

0.354772

0.67851

0.088156

1.73237

0.055017

1.50525

0.069288

8

6

11.7

58016.61

6.63

0

0.095

0.78155

0.42939

0.823224

0.347534

1.28195

0.499773

1.13111

0.641287

5

5

13.2

39055.46

8.38

0

0.36

0.899724

0.689422

1.63505

0.003863

0.964722

0.820913

1.31529

0.258151

4

4

8.7

56149.5

6.78

0

0.167

0.80474

0.475481

0.980631

0.915277

0.991937

0.887229

1.42427

0.127457

3

3

4.5

82556.85

9.35

5

0.015

0.75541

0.380685

1.15684

0.477072

0.817636

0.494372

1.24399

0.382443

12 4

6 3

18.2 5.0

39842.65 41884.52

5.06 8.37

0 0

0.21 0.043

0.727537 0.756912

0.332663 0.383387

0.924678 1.63863

0.687324 0.003668

0.933763 0.734117

0.747027 0.345747

1.00226 1.04095

0.999408 0.888328

2

2

4.1

46135.27

5.7

0

0.158

0.754496

0.379045

1.35396

0.107653

0.987337

0.875951

1.68155

0.014167

2

1

5.3

22975.82

5.11

0

0.308

0.621006

0.186543

0.807599

0.306748

1.17444

0.705467

1.40043

0.150397

4

2

13.3

27840.93

8.58

1

0.396

0.897794

0.684728

1.02065

0.927741

0.622983

0.197687

0.818808

0.411588

4

3

22.1

23407.13

5.12

0

0.73

0.815806

0.498398

0.791948

0.269206

0.590168

0.164491

0.586462

0.062576

2

1

2.7

29970.08

6.61

0

1.035

0.792827

0.451473

0.848309

0.419878

0.88916

0.644696

0.970889

0.888928

1

1

3.4

42680.31

4.73

0

0.583

0.85673

0.587991

0.728396

0.149526

1.42294

0.287225

1.04269

0.88339

1

1

1.0

8.97

0

0.999

0.642338

0.211165

0.673361

0.083193

0.744134

0.361903

0.649239

0.113901

10

4

21.3

23602.83

9.15

0

0.372

0.737138

0.348743

0.852526

0.432854

1.17501

0.704297

1.09389

0.740265

7

5

21.7

34580.89

8.63

0

0.039

0.765555

0.399171

1.04161

0.852303

0.761865

0.391636

1.01572

0.960662

2

1

1.8

72017.42

8.33

0

0.286

0.584189

0.149143

0.886243

0.544592

0.533913

0.117604

0.599119

0.071

1

1

2.5

64892.84

8.42

0

0.298

0.854499

0.582922

2.10693

4.70E07

0.518289

0.106646

1.97707

0.000432

1

1

15.4

11317.51

5.76

0

0.442

0.858564

0.592176

1.0286

0.899012

1.33062

0.418363

1.6864

0.013492

1

1

4.1

34397.52

9.49

0

0.094

0.989527

0.918106

0.804655

0.299434

0.711727

0.311329

0.727356

0.218368

3

2

3.1

95772.8

8.11

7

0.08

0.743367

0.359435

0.83879

0.391441

0.931781

0.742369

0.788873

0.33946

15

11

16.9

80971.85

6.18

1

0.195

0.766096

0.40017

1.0726

0.743436

0.863429

0.588445

1.13485

0.631659

1

1

1.5

51710.15

8.5

0

0.055

1.14766

0.745691

0.912939

0.64221

1.01178

0.936118

1.06722

0.814021

117018.8

0.39

53

(continued on next page)

No. of Pages 73

DRS7B_RAT

13

NSC 16186

Q6AYS2_RAT

34

22 April 2015

ES1_RAT

ATP synthase gamma chain OS = Rattus norvegicus GN = Taf3 PE = 2 SV = 1 ES1 protein homolog, mitochondrial OS = Rattus norvegicus PE = 1 SV = 2 RCG24191 OS = Rattus norvegicus GN = Sfxn1 PE = 2 SV = 1 cAMP-dependent protein kinase type II-beta regulatory subunit OS = Rattus norvegicus GN = Prkar2b PE = 1 SV = 3 Peroxiredoxin-5, mitochondrial OS = Rattus norvegicus GN = Prdx5 PE = 1 SV = 1 Inositol-trisphosphate 3-kinase A OS = Rattus norvegicus GN = Itpka PE = 1 SV = 3 Protein Appl1 OS = Rattus norvegicus GN = Appl1 PE = 4 SV = 1 Actin related protein 2/3 complex, subunit 4 (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Arpc4 PE = 2 SV = 1 Chaperonin containing Tcp1, subunit 6A (Zeta 1) OS = Rattus norvegicus GN = Cct6a PE = 2 SV = 1 Cytosolic acyl coenzyme A thioester hydrolase OS = Rattus norvegicus GN = Acot7 PE = 2 SV = 1 Cytosol aminopeptidase OS = Rattus norvegicus GN = Lap3 PE = 1 SV = 1 ATP-binding cassette sub-family B member 7, mitochondrial OS = Rattus norvegicus GN = Abcb7 PE = 2 SV = 1 Enolase (Fragment) OS = Rattus norvegicus PE = 3 SV = 1 3-ketoacyl-CoA thiolase, mitochondrial OS = Rattus norvegicus GN = Acaa2 PE = 3 SV = 1 Alpha-1-antiproteinase OS = Rattus norvegicus GN = Serpina1 PE = 1 SV = 2 Ras-related protein Rab-18 OS = Rattus norvegicus GN = Rab18 PE = 2 SV = 1 Vesicle-associated membrane protein-associated protein A OS = Rattus norvegicus GN = Vapa PE = 1 SV = 3 Rho GDP-dissociation inhibitor 1 OS = Rattus norvegicus GN = Arhgdia PE = 1 SV = 1 LIM and SH3 domain protein 1 OS = Rattus norvegicus GN = Lasp1 PE = 1 SV = 1 E3 ubiquitin-protein ligase RNF34 OS = Rattus norvegicus GN = Rnf34 PE = 1 SV = 1 Protein Plekha7 OS = Rattus norvegicus GN = Plekha7 PE = 2 SV = 1 RAB8B, member RAS oncogene family OS = Rattus norvegicus GN = Rab8b PE = 2 SV = 1 Fumarylacetoacetate hydrolase domain-containing protein 2 OS = Rattus norvegicus GN = Fahd2 PE = 1 SV = 1 GTP-binding protein 1 OS = Rattus norvegicus GN = Gtpbp1 PE = 2 SV = 1 Vacuolar protein sorting-associated protein 45 OS = Rattus norvegicus GN = Vps45 PE = 2 SV = 1 Ig lambda-2 chain C region OS = Rattus norvegicus PE = 2 SV = 1 Isoform 2 of Dehydrogenase/reductase SDR family member 7B OS = Rattus norvegicus GN = Dhrs7b Metabotropic glutamate receptor 2 OS = Rattus norvegicus GN = Grm2 PE = 1 SV = 1 Glycerol-3-phosphate dehydrogenase, mitochondrial OS = Rattus norvegicus GN = Gpd2 PE = 1 SV = 1 AarF domain containing kinase 1 (Predicted) OS = Rattus norvegicus GN = Adck1 PE = 4 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

Q6QI09_RAT

F1LSM5_RAT Q45QL6_RAT ANS1B_RAT HCDH_RAT CSN2_RAT TM9S2_RAT D3ZUP5_RAT

KKCC2_RAT TEN2_RAT D3ZT90_RAT D4A3N4_RAT PUR9_RAT NCEH1_RAT EF2_RAT Q45QL2_RAT SYGP1_RAT Q5XI17_RAT Q32PX6_RAT LDHA_RAT F1LW77_RAT RAB14_RAT FAHD1_RAT AOFB_RAT

RAB3C_RAT PAK1_RAT

33632.53

9.42

0

0.566

0.894537

0.676836

1.04379

0.844513

1.24702

0.562989

1.94049

0.000705

13

6

12.8

50113.26

9.1

0

0.252

0.855718

0.58569

1.22702

0.302711

0.805451

0.470767

1.39555

0.155452

5

4

8.1

59657.56

8.21

0

0.087

0.820378

0.508036

0.792898

0.271392

0.95494

0.797362

0.822111

0.420069

4

4

4.1

6.22

0

0.095

0.790184

0.44624

0.828922

0.36323

0.774734

0.414118

0.853789

0.506461

39

9

31.0

35003.07

5.91

0

0.186

0.718087

0.317311

0.757998

0.198947

0.985546

0.871567

1.07097

0.803528

9

7

13.9

57805.14

7.3

0

0.475

0.71814

0.317396

0.77548

0.233246

0.777948

0.419849

0.863696

0.53528

2

2

5.7

34447.41

8.83

0

0.142

0.829555

0.527669

0.903174

0.605653

0.971367

0.837007

1.11032

0.69591

3

3

7.7

51596.1

5.36

0

0.635

0.764322

0.396895

1.03697

0.868926

0.847894

0.555621

1.08345

0.768877

2

2

3.3

75551.49

7.22

0

0.267

0.780368

0.427112

1.04248

0.849185

0.806971

0.473678

1.03593

0.902677

1

1

10.7

8760.82

5.35

0

0.581

0.764106

0.396497

0.837703

0.388271

0.964296

0.819885

1.04509

0.876547

3

3

4.2

82487.69

6.28

0

0.592

0.797487

0.460781

1.0105

0.964532

0.951635

0.789446

1.25868

0.354237

1

1

1.8

66490.29

6.11

0

0.34

0.845783

0.56331

1.02536

0.910702

0.854335

0.569121

1.14709

0.600576

1

1

0.3

307470.6

6.28

1

0.382

1.30035

0.475096

0.718292

0.134998

1.11908

0.821923

1.27402

0.326205

3

3

10.3

49712.7

8.95

0

0.193

0.715157

0.312647

1.14006

0.525708

0.993712

0.891588

1.30706

0.27087

1

1

1.3

123398.4

8.8

0

0.105

1.14477

0.751266

1.10666

0.629498

0.967954

0.828733

1.28505

0.306971

1

1

2.2

64207.66

6.69

0

0.064

0.769044

0.40565

1.67596

0.002102

0.776368

0.417025

1.78684

0.00461

3

3

9.3

45821.25

6.56

1

0.007

0.851235

0.57554

1.28784

0.190993

0.886887

0.639637

1.55566

0.045661

5

4

6.2

95282.97

6.41

0

0.206

0.748959

0.369207

0.828095

0.360926

0.879499

0.623313

0.942902

0.790962

24

5

20.3

34383.41

6.24

0

0.145

0.70249

0.293005

0.746008

0.177656

0.864518

0.590778

0.960171

0.851125

24

12

12.2

9.18

0

0.596

0.736711

0.348017

0.887864

0.550301

0.729726

0.338813

0.760647

0.279383

2

2

2.5

64118.31

7.89

0

0.657

0.797054

0.459912

2.3531

7.30E10

0.568823

0.14527

1.94015

0.000708

5

3

20.9

21308.27

8.41

0

0.213

0.753586

0.377417

1.0684

0.757942

0.922927

0.72167

0.936932

0.770429

4

4

9.0

36450.08

8.45

0

0.064

0.831309

0.531465

0.765673

0.213522

0.908404

0.688161

0.961306

0.855113

4

2

10.6

29518.68

8.94

0

0.232

0.760353

0.389624

0.684167

0.093882

0.986254

0.873299

0.900798

0.650029

9

5

27.4

23926.7

5.85

0

0.411

0.72226

0.324032

0.740665

0.168735

0.661776

0.242954

0.609786

0.078801

1

1

6.3

24480.13

7.61

0

0.128

0.940351

0.790735

0.946912

0.775777

0.75066

0.372677

0.868922

0.550807

19

9

21.0

58458.06

8.47

0

0.166

0.783345

0.432861

1.18288

0.406763

0.735864

0.348531

1.20481

0.464194

1

1

2.1

88729.95

6.82

11

0.218

0.878186

0.637763

0.809234

0.310861

1.11526

0.83013

1.41398

0.137001

19

6

35.2

25871.82

5.1

0

0.523

0.678539

0.258175

0.799369

0.286594

1.00733

0.925111

1.01236

0.970324

3

3

7.9

60577.13

5.63

0

0.607

0.831819

0.532571

0.994366

0.973117

0.882527

0.62998

1.16972

0.545009

121235

144720.4

No. of Pages 73

CLCN7_RAT

3.4

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

F1M3T0_RAT

1

NSC 16186

D4AC23_RAT

1

22 April 2015

EF1A1_RAT

Protein Mrpl19 OS = Rattus norvegicus GN = Mrpl19 PE = 4 SV = 1 Elongation factor 1-alpha 1 OS = Rattus norvegicus GN = Eef1a1 PE = 1 SV = 1 Protein Cct7 OS = Rattus norvegicus GN = Cct7 PE = 3 SV = 1 Nck-associated protein 1 OS = Rattus norvegicus GN = Nckap1 PE = 2 SV = 1 Guanine nucleotide binding protein beta 2 (Fragment) OS = Rattus norvegicus GN = Gnb2 PE = 2 SV = 1 Isoform 3 of Ankyrin repeat and sterile alpha motif domaincontaining protein 1B OS = Rattus norvegicus GN = Anks1b Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial OS = Rattus norvegicus GN = Hadh PE = 2 SV = 1 COP9 signalosome complex subunit 2 OS = Rattus norvegicus GN = Cops2 PE = 2 SV = 1 Transmembrane 9 superfamily member 2 OS = Rattus norvegicus GN = Tm9sf2 PE = 2 SV = 1 Protein Brk1 OS = Rattus norvegicus GN = Brk1 PE = 4 SV = 1 ARF GTPase-activating protein GIT1 (Fragment) OS = Rattus norvegicus GN = Git1 PE = 2 SV = 1 Calcium/calmodulin-dependent protein kinase kinase 2 OS = Rattus norvegicus GN = Camkk2 PE = 2 SV = 1 Teneurin-2 OS = Rattus norvegicus GN = Tenm2 PE = 1 SV = 2 Glutaryl-Coenzyme A dehydrogenase (Predicted) OS = Rattus norvegicus GN = Gcdh PE = 3 SV = 1 Protein Adcy1 OS = Rattus norvegicus GN = Adcy1 PE = 3 SV = 1 Bifunctional purine biosynthesis protein PURH OS = Rattus norvegicus GN = Atic PE = 1 SV = 2 Neutral cholesterol ester hydrolase 1 OS = Rattus norvegicus GN = Nceh1 PE = 2 SV = 1 Elongation factor 2 OS = Rattus norvegicus GN = Eef2 PE = 1 SV = 4 Guanine nucleotide binding protein beta 4 (Fragment) OS = Rattus norvegicus GN = Gnb4 PE = 2 SV = 1 Ras GTPase-activating protein SynGAP OS = Rattus norvegicus GN = Syngap1 PE = 1 SV = 2 Protein Tarsl2 OS = Rattus norvegicus GN = Tarsl2 PE = 2 SV = 1 Protein Rhog OS = Rattus norvegicus GN = Rhog PE = 2 SV = 1 L-lactate dehydrogenase A chain OS = Rattus norvegicus GN = Ldha PE = 1 SV = 1 Protein Rab33b (Fragment) OS = Rattus norvegicus GN = Rab33b PE = 3 SV = 1 Ras-related protein Rab-14 OS = Rattus norvegicus GN = Rab14 PE = 1 SV = 3 Acylpyruvase FAHD1, mitochondrial OS = Rattus norvegicus GN = Fahd1 PE = 2 SV = 1 Amine oxidase [flavin-containing] B OS = Rattus norvegicus GN = Maob PE = 1 SV = 3 H(+)/Cl(-) exchange transporter 7 OS = Rattus norvegicus GN = Clcn7 PE = 2 SV = 1 Ras-related protein Rab-3C OS = Rattus norvegicus GN = Rab3c PE = 1 SV = 1 Serine/threonine-protein kinase PAK 1 OS = Rattus norvegicus GN = Pak1 PE = 1 SV = 3

54

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

D4A4A9_RAT

Q7TP54_RAT RS15A_RAT ENPL_RAT Q9JMA8_RAT Q9QZX1_RAT MPPB_RAT G3V7X2_RAT TBA8_RAT SC31A_RAT ACADL_RAT TXD12_RAT NDUF4_RAT

F1LQ63_RAT KCNA2_RAT Q4G079_RAT CAND1_RAT ECSIT_RAT

F1LVC6_RAT PHOCN_RAT B2RZA9_RAT B0BNB9_RAT D3ZUL1_RAT VATC1_RAT

D3ZGN0_RAT PYRD_RAT

6.6

83000.85

4.53

2

0.377

0.833346

0.535891

1.09954

0.652685

1.03067

0.982879

1.16726

0.550916

1

1

2.3

55069.78

9.06

0

0.737

1.03447

0.971814

1.44897

0.041197

0.743926

0.361563

1.41456

0.136451

6

4

46.0

12650.61

9.78

1

0.22

0.900965

0.692445

0.982871

0.924685

0.701616

0.296554

1.07474

0.793009

3

2

1.8

5.31

0

0.409

0.652044

0.223114

0.913534

0.644467

0.910654

0.693315

1.04031

0.890156

1

1

6.9

14839.34

10.14

0

0.12

0.723927

0.326742

1.29683

0.177465

0.8087

0.477

1.49021

0.078027

11

8

10.6

92769.86

4.72

0

0.732

0.743735

0.360073

1.09606

0.664154

0.859151

0.579317

1.2196

0.432263

1

1

1.0

104442.6

6.07

1

0.212

0.911548

0.718428

1.17884

0.417245

0.714865

0.316012

1.06776

0.812512

1

1

1.1

77438.3

4.59

0

1.143

0.774155

0.415256

0.975121

0.892179

0.89131

0.649496

1.18838

0.501175

1

1

2.0

54264.59

6.26

0

0.164

0.731599

0.339406

1.12994

0.55621

0.674328

0.259052

0.882396

0.591837

1

1

2.1

71000.39

4.71

0

0.949

0.799837

0.465516

1.07697

0.728425

0.783913

0.430608

1.32635

0.241721

32

11

25.4

50036.93

4.98

0

0.209

0.794342

0.454487

1.10079

0.648584

0.820558

0.500125

1.34612

0.214203

1

1

1.1

6.26

0

0.398

0.749685

0.370489

0.799289

0.286404

1.33112

0.417574

1.03284

0.911515

144707.1

133432.2

4

3

7.4

47872.31

7.63

0

0.223

0.783268

0.432712

1.20786

0.345494

0.86837

0.599069

1.60344

0.029929

1

1

8.8

19018.36

5.25

0

0.314

0.93053

0.765841

0.82396

0.349537

0.781089

0.425495

0.928911

0.743098

2

2

12.1

20157.92

8.98

0

0.735

0.674969

0.253239

0.906068

0.616389

0.871012

0.604785

1.08629

0.761077

19

9

9.7

4.82

0

0.337

0.728442

0.334157

0.837878

0.388779

0.876966

0.617757

0.958467

0.845144

4

3

11.6

56700.13

4.77

5

0.035

0.754947

0.379854

1.10925

0.621137

0.561742

0.139289

0.774375

0.307636

2

2

10.5

34573.52

8.52

0

0.48

0.711495

0.306881

1.09725

0.660244

0.769924

0.405627

1.13461

0.63227

3

3

2.4

5.52

0

0.019

0.721973

0.323567

0.889142

0.554825

0.842944

0.545353

0.992156

0.964611

1

1

1.6

49619.09

5.99

0

0.468

0.858138

0.591204

0.93149

0.714036

0.999176

0.905023

1.41975

0.131587

1

1

6.3

23008.62

5.86

0

0.06

0.766647

0.401191

1.09644

0.662918

0.766086

0.398927

1.13191

0.639221

1

1

6.7

26032.16

5.5

0

0.492

0.691278

0.276325

0.908605

0.625872

0.483825

0.085335

0.594726

0.067977

1

1

5.9

17818.23

7.64

0

0.75

0.85477

0.583537

0.984197

0.93026

0.655008

0.234572

0.901387

0.651929

3

2

5.9

49093.73

9.51

1

0.018

0.740614

0.354684

1.01261

0.956857

1.17597

0.70233

1.44599

0.109016

1

1

10.1

25317.48

9.62

0

1.3

1.05278

0.93459

0.450722

0.003607

0.535045

0.118431

0.286192

0.001338

9

5

9.2

43900.02

7.02

0

0.305

0.75157

0.373826

1.02043

0.928536

0.646186

0.223957

1.01348

0.967106

7

4

25.1

23614.37

8.32

0

0.42

0.809164

0.484574

0.971227

0.875913

0.783503

0.429864

1.1718

0.540033

1

1

0.6

8.17

0

0.503

0.913012

0.72205

0.908196

0.624337

0.981798

0.862404

1.24856

0.373535

1

1

3.8

9.45

1

0.147

0.795556

0.45691

1.03742

0.867302

0.786329

0.435012

1.12572

0.655276

149518.6

136360.2

147898.2 42662.39

55

(continued on next page)

No. of Pages 73

O88565_RAT

3

NSC 16186

B2RYT5_RAT

5

22 April 2015

FA98A_RAT

Reticulon-1 OS = Rattus norvegicus GN = Rtn1 PE = 2 SV = 1 Protein FAM98A OS = Rattus norvegicus GN = Fam98a PE = 2 SV = 1 Cox7a2l protein OS = Rattus norvegicus GN = Cox7a2l PE = 4 SV = 1 Ab2-162 OS = Rattus norvegicus GN = Fam65b PE = 2 SV = 1 40S ribosomal protein S15a OS = Rattus norvegicus GN = Rps15a PE = 1 SV = 2 Endoplasmin OS = Rattus norvegicus GN = Hsp90b1 PE = 1 SV = 2 Exostoses (Multiple)-like 3, isoform CRA_a OS = Rattus norvegicus GN = Extl3 PE = 2 SV = 1 Nucleolin-related protein NRP OS = Rattus norvegicus GN = Norp PE = 2 SV = 1 Mitochondrial-processing peptidase subunit beta OS = Rattus norvegicus GN = Pmpcb PE = 1 SV = 3 Secretogranin 2, isoform CRA_a OS = Rattus norvegicus GN = Scg2 PE = 4 SV = 1 Tubulin alpha-8 chain OS = Rattus norvegicus GN = Tuba8 PE = 2 SV = 1 Protein transport protein Sec31A OS = Rattus norvegicus GN = Sec31a PE = 4 SV = 1 Long-chain specific acyl-CoA dehydrogenase, mitochondrial OS = Rattus norvegicus GN = Acadl PE = 1 SV = 1 Thioredoxin domain-containing protein 12 OS = Rattus norvegicus GN = Txndc12 PE = 2 SV = 2 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 4 OS = Rattus norvegicus GN = Ndufaf4 PE = 1 SV = 1 Tenascin-R OS = Rattus norvegicus GN = Tnr PE = 2 SV = 1 Potassium voltage-gated channel subfamily A member 2 OS = Rattus norvegicus GN = Kcna2 PE = 1 SV = 1 Protein Aimp1 OS = Rattus norvegicus GN = Aimp1 PE = 2 SV = 1 Cullin-associated NEDD8-dissociated protein 1 OS = Rattus norvegicus GN = Cand1 PE = 1 SV = 1 Evolutionarily conserved signaling intermediate in Toll pathway, mitochondrial OS = Rattus norvegicus GN = Ecsit PE = 2 SV = 1 Glutathione S-transferase OS = Rattus norvegicus GN = LOC100365881 PE = 2 SV = 1 MOB-like protein phocein OS = Rattus norvegicus GN = Mob4 PE = 1 SV = 1 Protein Ube2l3 OS = Rattus norvegicus GN = Ube2l3 PE = 2 SV = 1 HtrA serine peptidase 2 OS = Rattus norvegicus GN = Htra2 PE = 2 SV = 1 Protein Ccdc124 OS = Rattus norvegicus GN = Ccdc124 PE = 4 SV = 1 V-type proton ATPase subunit C 1 OS = Rattus norvegicus GN = Atp6v1c1 PE = 2 SV = 1 Protein Rab5a OS = Rattus norvegicus GN = Rab5a PE = 2 SV = 1 Protein Tbc1d4 OS = Rattus norvegicus GN = Tbc1d4 PE = 2 SV = 1 Dihydroorotate dehydrogenase (quinone), mitochondrial OS = Rattus norvegicus GN = Dhodh PE = 1 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

RTN1_RAT

F1LNE8_RAT D3ZLT1_RAT

CD9_RAT SIR2_RAT IQEC3_RAT ADT2_RAT D4A0A1_RAT

D3ZF13_RAT DHPR_RAT DDX1_RAT ST4A1_RAT D3ZAN1_RAT C9WPN7_RAT NUDT9_RAT FUT8_RAT PLD3_RAT Q6P503_RAT RAB3A_RAT G3V624_RAT Q4V8H2_RAT RL14_RAT JPH2_RAT

F1LUM5_RAT HBB2_RAT MYPR_RAT

60602.06

6.35

0

0.363

0.872307

0.623949

1.2677

0.224013

0.62797

0.203135

0.747454

0.253943

5

3

9.3

44447.85

5.62

0

0.416

0.77451

0.415927

1.28768

0.191238

0.533233

0.117109

0.987567

0.94823

13

5

13.6

41020.81

9.11

0

0.269

0.704729

0.296416

0.984188

0.930225

0.799826

0.460083

1.02702

0.928187

2

2

5.8

51121.41

9.21

0

0.11

0.756562

0.382755

0.852035

0.431331

0.824569

0.508079

0.925656

0.732097

6

3

23.4

16567.79

8.69

0

1.102

0.765723

0.399481

0.990995

0.958894

0.775937

0.416257

1.09639

0.733459

5

2

10.2

25214.65

6.93

4

0.537

0.790075

0.446024

0.584648

0.027671

0.710093

0.30891

0.663898

0.129717

6

4

12.4

43025.58

5.32

0

0.402

0.805667

0.477378

0.808521

0.309064

0.79256

0.446487

1.05242

0.855723

2

2

1.5

5.84

0

0.406

1.03795

0.964738

1.16513

0.45399

1.02796

0.976157

1.35434

0.203464

54

15

34.6

9.74

2

0.021

0.680165

0.260445

0.915657

0.652545

0.84809

0.556029

1.06093

0.8317

3

2

2.3

5.83

0

0.719692

0.319885

1.11553

0.601076

0.770261

0.406217

1.01096

0.974355

2

1

3.5

28863.43

9.03

0

0.112

1.02485

0.991415

1.24094

0.273931

0.648514

0.226724

0.576568

0.056582

1

1

5.8

17514.29

4.93

0

0.038

0.66145

0.235149

1.09853

0.656021

0.777438

0.418936

1.14512

0.605523

10

4

27.0

25551.92

7.67

0

0.034

0.731987

0.340055

0.885269

0.541174

0.674635

0.259454

0.958692

0.845931

2

1

2.4

82496.19

6.8

0

0.399

0.656479

0.228732

0.773331

0.228817

0.791603

0.444714

0.664574

0.130485

1

1

2.8

33053.48

5.32

0

0.338

0.648441

0.218624

0.864518

0.470998

0.754212

0.378625

1.00354

0.995741

1

1

1.0

6.89

0

0.302

1.03917

0.962261

1.41103

0.061659

0.798728

0.458015

1.6799

0.014404

1

1

5.9

29589.08

7.2

0

0.056

0.660908

0.234443

0.699922

0.111409

1.06049

0.949554

1.20688

0.459662

1

1

3.4

38561.71

6.61

0

0.635

0.621058

0.186599

0.857304

0.447836

0.840006

0.539303

1.09448

0.738641

1

1

2.4

66483.87

7.13

1

0.557

0.722619

0.324614

1.00863

0.971327

0.772391

0.409968

0.994199

0.971909

1

1

2.5

54398.5

6.07

1

0.153

0.727927

0.333306

1.49217

0.0252

0.84073

0.540791

1.20776

0.457731

6

3

8.9

28308.58

9.44

0

0.453

0.717316

0.31608

1.12855

0.56046

0.953418

0.793713

1.12529

0.656403

28

9

47.3

24969.6

4.85

0

0.49

0.742253

0.357508

0.835992

0.38331

0.733141

0.344199

0.904732

0.662769

1

1

2.1

53177.34

6.65

0

0.346

0.569411

0.135854

0.735563

0.160533

1.01997

0.956377

1.17418

0.534346

1

1

1.3

76670.18

5.51

0

0.407

1.1952

0.655788

0.96368

0.844538

1.09325

0.877823

1.15216

0.58791

3

2

12.2

23338.54

11.11

0

0.492

0.755608

0.381041

0.989274

0.951638

0.841183

0.541722

1.1443

0.607589

1

1

1.3

74257.62

8.43

1

0.791

0.662461

0.236469

0.806309

0.303529

0.939489

0.760541

1.0909

0.748416

13

3

6.8

56117.62

7.16

0

0.396

0.700789

0.290432

0.854689

0.4396

0.874691

0.612787

1.08613

0.761511

10

6

9.7

49891.37

5.47

0

0.118

0.769252

0.406039

1.41522

0.059047

0.657918

0.23815

1.44166

0.112518

33

10

74.2

15982.24

8.91

0

0.003

0.761825

0.392311

1.9311

2.26E05

0.785523

0.433539

2.69229

1.05E09

50

7

24.6

30076.85

8.71

1

0.55

0.690373

0.275009

0.591181

0.030209

1.04038

0.993824

0.92671

0.735654

129016.6 32900.87 103024.8

104475.5

0.83

No. of Pages 73

Q499T3_RAT

3.8

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

TOMT_RAT

2

NSC 16186

KCAB2_RAT

2

22 April 2015

SHLB2_RAT

EH domain-containing protein 1 OS = Rattus norvegicus GN = Ehd1 PE = 1 SV = 1 Endophilin-B2 OS = Rattus norvegicus GN = Sh3glb2 PE = 2 SV = 1 Voltage-gated potassium channel subunit beta-2 OS = Rattus norvegicus GN = Kcnab2 PE = 1 SV = 1 Gamma-aminobutyric acid receptor subunit alpha-2 OS = Rattus norvegicus GN = Gabra2 PE = 2 SV = 1 NADH dehydrogenase (Ubiquinone) 1 beta subcomplex, 7 (Predicted) OS = Rattus norvegicus GN = Ndufb7 PE = 4 SV = 1 CD9 antigen OS = Rattus norvegicus GN = Cd9 PE = 1 SV = 2 NAD-dependent protein deacetylase sirtuin-2 OS = Rattus norvegicus GN = Sirt2 PE = 2 SV = 1 IQ motif and SEC7 domain-containing protein 3 OS = Rattus norvegicus GN = Iqsec3 PE = 1 SV = 1 ADP/ATP translocase 2 OS = Rattus norvegicus GN = Slc25a5 PE = 1 SV = 3 Protein LOC100363805 OS = Rattus norvegicus GN = Soga3 PE = 4 SV = 1 Transmembrane O-methyltransferase OS = Rattus norvegicus GN = Tomt PE = 2 SV = 1 Acyl carrier protein OS = Rattus norvegicus GN = LOC683884 PE = 3 SV = 1 Dihydropteridine reductase OS = Rattus norvegicus GN = Qdpr PE = 1 SV = 1 ATP-dependent RNA helicase DDX1 OS = Rattus norvegicus GN = Ddx1 PE = 2 SV = 1 Sulfotransferase 4A1 OS = Rattus norvegicus GN = Sult4a1 PE = 2 SV = 1 Type I inositol 3,4-bisphosphate 4-phosphatase OS = Rattus norvegicus GN = Inpp4a PE = 2 SV = 1 Eif2s3y (Fragment) OS = Rattus norvegicus GN = Eif2s3y PE = 2 SV = 1 ADP-ribose pyrophosphatase, mitochondrial OS = Rattus norvegicus GN = Nudt9 PE = 2 SV = 1 Alpha-(1,6)-fucosyltransferase OS = Rattus norvegicus GN = Fut8 PE = 2 SV = 1 Phospholipase D3 OS = Rattus norvegicus GN = Pld3 PE = 2 SV = 1 ATPase, H+ transporting, V1 subunit D, isoform CRA_c OS = Rattus norvegicus GN = Atp6v1d PE = 2 SV = 1 Ras-related protein Rab-3A OS = Rattus norvegicus GN = Rab3a PE = 1 SV = 1 Coronin OS = Rattus norvegicus GN = Coro1c PE = 3 SV = 1 SEC3-like 1 (S. cerevisiae) OS = Rattus norvegicus GN = Sec3l1 PE = 2 SV = 1 60S ribosomal protein L14 OS = Rattus norvegicus GN = Rpl14 PE = 1 SV = 3 Junctophilin-2 OS = Rattus norvegicus GN = Jph2 PE = 2 SV = 1 Sirpa protein OS = Rattus norvegicus GN = Sirpa PE = 2 SV = 1 Protein Tubal3 (Fragment) OS = Rattus norvegicus GN = Tubal3 PE = 3 SV = 1 Hemoglobin subunit beta-2 OS = Rattus norvegicus PE = 1 SV = 2 Myelin proteolipid protein OS = Rattus norvegicus GN = Plp1 PE = 1 SV = 2

56

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

EHD1_RAT

D3ZRH1_RAT HPCA_RAT EXOC8_RAT Q62669_RAT OS9_RAT D3ZVI9_RAT

D3ZRC4_RAT

FSCN1_RAT D3ZDP2_RAT CPLX1_RAT F1LRZ7_RAT D3ZCI5_RAT DYN3_RAT DCTN2_RAT ABCB8_RAT NDUS4_RAT

Q6TXF3_RAT FKBP4_RAT HPT_RAT RAB3D_RAT SCN8A_RAT Q5XI34_RAT

FRS1L_RAT CAP1_RAT

1.2

87715.71

5.3

0

0.666

0.865589

0.608326

0.95327

0.801673

1.37343

0.35367

1.46022

0.098133

1

1

4.2

29197.86

10.28

0

0.317

0.888324

0.661879

1.00292

0.992042

0.915452

0.70435

1.08278

0.770724

35

10

75.5

15979.19

7.87

0

0.042

0.758063

0.385467

1.72359

0.000993

0.807122

0.473967

2.24838

6.82E06

1

1

2.1

48022.64

9.76

0

0.034

0.966595

0.85824

0.969021

0.866718

0.856627

0.573963

1.39452

0.156545

6

3

12.4

22427.16

4.87

0

0.56

0.69395

0.280241

1.19066

0.387019

0.894987

0.657736

1.04423

0.879007

1

1

2.0

81042.33

5.3

0

0.392

0.586052

0.150886

1.17647

0.423479

0.62568

0.200619

1.09338

0.741643

18

5

32.0

16022.32

7.93

0

0.001

0.757825

0.385037

2.13809

2.22E07

0.826309

0.51155

3.08147

6.06E14

1

1

1.5

75364.03

4.77

1

0.885

0.576102

0.141752

1.00909

0.969639

0.745199

0.363647

0.908435

0.674849

1

1

9.1

23263.18

6.36

0

0.156

0.83545

0.540482

1.07325

0.741193

0.655056

0.234631

1.21645

0.438945

1

1

2.3

87959.96

9.19

0

0.453

0.525464

0.1017

0.501816

0.008284

0.795555

0.452064

0.715128

0.198558

4

2

5.3

54490.36

6.29

0

0.424

0.782534

0.431291

0.812466

0.319098

0.999656

0.906203

0.989093

0.953676

2

2

14.6

23469.74

6

4

42.1

15143.98

13

7

7.1

1

1

6.3

10

5

2

0

0.677

0.539539

0.111802

0.644248

0.059226

1.04924

0.974314

0.935117

0.76422

5.02

0

1.22

0.81331

0.493178

0.834272

0.378363

0.715729

0.317311

0.612421

0.080833

5.71

0

1.029

0.662558

0.236597

0.71802

0.134623

0.903203

0.676304

1.00507

0.991319

21695.47

9.34

0

0.555

0.699235

0.288095

0.797143

0.2813

0.750781

0.372878

0.801124

0.36794

6.5

97894.97

8.19

0

0.466

0.756667

0.382946

0.93299

0.719969

0.562833

0.140197

0.813846

0.399041

1

2.2

44147.36

5.14

0

0.499

0.909429

0.713199

1.10944

0.620509

0.757989

0.385012

1.21313

0.446072

4

4

8.5

77769.52

9.61

4

0.149

0.60997

0.174669

0.95535

0.810195

0.730169

0.33951

1.20073

0.47324

8

3

18.3

19740.41

10.14

0

0.545

0.648629

0.218855

0.934727

0.726857

0.743034

0.360106

1.00808

0.982642

3

1

2.7

66448.74

8.94

0

0.576

0.718914

0.318635

0.942264

0.756998

0.359947

0.035254

0.642727

0.10738

1

1

3.3

51505.68

5.46

0

0.557

0.746036

0.364079

0.8405

0.396462

0.772939

0.410937

1.04579

0.874548

1

1

2.0

38562.75

6.1

0

0.257

0.82602

0.52006

1.19066

0.38701

0.783353

0.429591

1.38409

0.167846

13

4

21.5

24289.94

4.75

0

0.363

0.680241

0.260551

0.79552

0.277483

0.838832

0.536894

0.991753

0.963172

2

2

1.5

5.93

0

0.055

1.66086

0.102111

1.39243

0.074419

0.683838

0.271729

0.813095

0.397162

6

4

7.1

65321.88

5

0

0.075

0.685092

0.267407

0.960344

0.830748

0.782268

0.427625

1.09448

0.738644

2

2

4.2

48443.08

9.58

1

0.448

0.734648

0.344525

1.10817

0.62462

0.682103

0.269386

0.989952

0.956744

5

3

13.7

32456.22

5.22

0

0.287

0.622417

0.188102

0.683095

0.092774

1.05466

0.962381

0.925394

0.731213

3

3

6.8

51588.29

7.16

0

0.352

0.657606

0.230176

0.840079

0.395223

0.838932

0.537099

1.18542

0.508002

114410.5

211394.1

10.2

57

(continued on next page)

No. of Pages 73

B0BN02_RAT

1

NSC 16186

HBB1_RAT

1

22 April 2015

D3ZX01_RAT

Protein Sec63 OS = Rattus norvegicus GN = Sec63 PE = 2 SV = 1 Protein Rps4y2 OS = Rattus norvegicus GN = Rps4y2 PE = 4 SV = 1 Hemoglobin subunit beta-1 OS = Rattus norvegicus GN = Hbb PE = 1 SV = 3 Protein Oxa1l OS = Rattus norvegicus GN = Oxa1l PE = 3 SV = 1 Neuron-specific calcium-binding protein hippocalcin OS = Rattus norvegicus GN = Hpca PE = 1 SV = 2 Exocyst complex component 8 OS = Rattus norvegicus GN = Exoc8 PE = 1 SV = 1 Protein Hbb-b1 OS = Rattus norvegicus GN = Hbb-b1 PE = 3 SV = 1 Protein OS-9 OS = Rattus norvegicus GN = Os9 PE = 1 SV = 1 Parkinson disease 7 domain containing 1 (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Pddc1 PE = 4 SV = 1 Similar to intracellular membrane-associated calciumindependent phospholipase A2 gamma (Predicted), isoform CRA_b OS = Rattus norvegicus GN = Pnpla8 PE = 4 SV = 1 Fascin OS = Rattus norvegicus GN = Fscn1 PE = 1 SV = 2 Protein Ict1 OS = Rattus norvegicus GN = Ict1 PE = 4 SV = 1 Complexin-1 (Fragment) OS = Rattus norvegicus GN = Cplx1 PE = 4 SV = 1 Neurofilament heavy polypeptide OS = Rattus norvegicus GN = Nefh PE = 2 SV = 1 Protein Stxbp6 OS = Rattus norvegicus GN = Stxbp6 PE = 4 SV = 1 Dynamin-3 OS = Rattus norvegicus GN = Dnm3 PE = 2 SV = 1 Dynactin subunit 2 OS = Rattus norvegicus GN = Dctn2 PE = 1 SV = 1 ATP-binding cassette sub-family B member 8, mitochondrial OS = Rattus norvegicus GN = Abcb8 PE = 2 SV = 1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial OS = Rattus norvegicus GN = Ndufs4 PE = 1 SV = 1 Acyl-CoA-binding protein OS = Rattus norvegicus GN = Dbi PE = 2 SV = 1 Peptidyl-prolyl cis-trans isomerase FKBP4 OS = Rattus norvegicus GN = Fkbp4 PE = 4 SV = 1 Haptoglobin OS = Rattus norvegicus GN = Hp PE = 1 SV = 3 GTP-binding protein Rab-3D OS = Rattus norvegicus GN = Rab3d PE = 1 SV = 2 Sodium channel protein type 8 subunit alpha (Fragment) OS = Rattus norvegicus GN = Scn8a PE = 2 SV = 1 Protein Ppp2r1a OS = Rattus norvegicus GN = Ppp2r1a PE = 2 SV = 1 Mtx1 protein OS = Rattus norvegicus GN = Mtx1 PE = 2 SV = 1 DOMON domain-containing protein FRRS1L OS = Rattus norvegicus GN = Frrs1l PE = 1 SV = 1 Adenylyl cyclase-associated protein 1 OS = Rattus norvegicus GN = Cap1 PE = 1 SV = 3

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

D4A2Z6_RAT

B4F774_RAT SCMC2_RAT Q9JLT5_RAT LYPA2_RAT D3ZJH5_RAT PEA15_RAT VP33A_RAT

Q45QM4_RAT

RYR2_RAT ETFA_RAT RASN_RAT RASH_RAT DNJC5_RAT DLGP1_RAT B2GV92_RAT SEPT8_RAT GTR8_RAT MK01_RAT Q45QK2_RAT

ACY1A_RAT DLG1_RAT D4AB01_RAT

B2CZC8_RAT MPRIP_RAT

80575.72

5.7

0

0.687

0.702503

0.293025

0.836624

0.385138

0.686822

0.275794

0.928393

0.741345

3

3

10.3

32941.35

9.4

0

-0.561

0.704193

0.295597

1.00449

0.986353

0.646312

0.224105

1.12692

0.652171

2

1

7.5

31753.75

6.99

0

0.281

0.603304

0.167776

0.354242

0.000623

0.364179

0.036413

0.308192

0.001877

5

3

11.0

35114.04

6.33

0

0.281

0.651236

0.222101

0.858698

0.452259

0.449544

0.067692

0.617432

0.084812

1

1

1.7

54179.2

8.84

0

0.117

0.604154

0.168643

1.08394

0.70471

0.754429

0.37899

1.27673

0.3214

3 1

3 1

3.9 7.8

100531.6 24806.75

8.24 6.74

9 0

0.032 0.135

0.670964 0.459292

0.247782 0.063541

0.952228 1.37735

0.797415 0.086278

0.527123 0.490575

0.112738 0.089213

0.872844 0.674662

0.562604 0.14238

1

1

4.9

29970.14

10.48

0

0.532

0.608517

0.173148

0.790086

0.264958

0.810045

0.479592

1.12871

0.647503

2

1

9.2

15039.91

4.93

0

0.644

0.870675

0.620137

2.78542

4.34E16

0.32032

0.025844

1.18851

0.500887

2

2

1.7

67512.95

6.6

0

0.248

1.06115

0.917606

0.982771

0.924265

0.696676

0.289509

1.19494

0.486226

11

9

9.8

6.41

0

0.325

0.618948

0.184284

0.912306

0.639812

0.691109

0.281706

0.836182

0.45733

13

5

20.0

5.46

0

0.577

0.62346

0.189261

0.893721

0.571181

1.24258

0.571297

1.77656

0.005174

4

4

1.0

5.73

0

0.31

0.607308

0.171891

0.652511

0.06536

0.610977

0.185015

0.675786

0.143754

2

1

3.0

34950.94

8.62

0

0.131

0.685673

0.268236

0.90843

0.625214

0.598436

0.17243

0.787168

0.335611

3

3

21.7

21242.97

5.02

0

0.317

0.570909

0.137158

0.650484

0.063808

0.557459

0.135764

0.598085

0.070278

5

5

24.5

26185.42

7.71

0

0.424

0.649964

0.220514

0.672876

0.082737

0.646842

0.224734

0.761843

0.281772

7

2

7.6

22100.52

4.93

0

0.483

0.717899

0.31701

0.884598

0.538824

0.72452

0.330709

0.936534

0.769065

2

2

3.1

6.75

0

0.771

0.654838

0.226642

0.73292

0.156404

0.798436

0.457466

0.98192

0.928105

2

1

10.6

18721.22

4.36

0

1.047

0.691474

0.276612

0.751967

0.188016

0.622262

0.19691

0.533186

0.035649

10

4

11.8

51251.47

5.74

0

0.679

0.724125

0.327065

0.785387

0.254448

1.15578

0.744093

1.37647

0.17649

1

1

2.5

51458.41

8.56

12

0.679

0.843115

0.557372

1.12181

0.581305

0.606092

0.180035

0.894228

0.628981

7

7

20.1

41178.01

6.5

0

0.289

0.673937

0.251825

0.900405

0.595461

0.672887

0.257167

1.10558

0.7086

1

1

43.9

4346.96

6.13

0

0.12

0.531481

0.105926

1.0501

0.822102

0.441993

0.06424

0.797647

0.359709

1

1

2.0

45803.53

6.03

0

0.292

0.518411

0.096919

0.94589

0.771638

0.731247

0.341205

1.08262

0.77119

5

5

5.9

5.67

0

0.551

0.659598

0.232743

0.69192

0.102208

0.706833

0.304119

0.694563

0.16826

5

1

9.2

17379.92

9.46

0

0.02

0.729129

0.335296

0.757914

0.198793

1.12223

0.815172

1.10558

0.708624

4

3

14.1

26624.57

6.27

0

0.712

0.627018

0.193256

0.832876

0.374378

0.703969

0.299951

1.0883

0.755541

2

2

1.6

131884

8.07

6

0.107

1.01531

0.985972

1.90447

3.85E05

0.831261

0.521499

1.38223

0.169928

1

1

1.5

118134.1

6.05

0

0.941

0.520921

0.098599

0.564996

0.021115

0.702252

0.297469

0.48112

0.019585

116710.7 38282.95

562334

109262.6

102788

No. of Pages 73

Q5FVS1_RAT

6.2

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

D3ZQD3_RAT

4

NSC 16186

LIS1_RAT

4

22 April 2015

Q5RK08_RAT

Beta-adducin OS = Rattus norvegicus GN = Add2 PE = 4 SV = 1 Glioblastoma amplified sequence OS = Rattus norvegicus GN = Gbas PE = 2 SV = 1 Platelet-activating factor acetylhydrolase IB subunit alpha (Fragment) OS = Rattus norvegicus GN = Pafah1b1 PE = 2 SV = 1 Protein Gdap1l1 OS = Rattus norvegicus GN = Gdap1l1 PE = 2 SV = 1 Calcium-binding mitochondrial carrier protein SCaMC-2 OS = Rattus norvegicus GN = Slc25a25 PE = 2 SV = 1 WFS1 OS = Rattus norvegicus GN = Wfs1 PE = 2 SV = 1 Acyl-protein thioesterase 2 OS = Rattus norvegicus GN = Lypla2 PE = 1 SV = 1 Protein RGD1562409 OS = Rattus norvegicus GN = RGD1562409 PE = 4 SV = 1 Astrocytic phosphoprotein PEA-15 OS = Rattus norvegicus GN = Pea15 PE = 1 SV = 1 Vacuolar protein sorting-associated protein 33A OS = Rattus norvegicus GN = Vps33a PE = 1 SV = 1 Oxoglutarate dehydrogenase-like (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Ogdhl PE = 4 SV = 1 Guanine nucleotide binding protein alpha q subunit (Fragment) OS = Rattus norvegicus GN = Gnaq PE = 2 SV = 1 Isoform 2 of Ryanodine receptor 2 OS = Rattus norvegicus GN = Ryr2 Electron transfer flavoprotein subunit alpha, mitochondrial OS = Rattus norvegicus GN = Etfa PE = 1 SV = 4 GTPase NRas OS = Rattus norvegicus GN = Nras PE = 1 SV = 1 Protein Hras (Fragment) OS = Rattus norvegicus GN = Hras PE = 4 SV = 1 DnaJ homolog subfamily C member 5 OS = Rattus norvegicus GN = Dnajc5 PE = 1 SV = 1 Disks large-associated protein 1 OS = Rattus norvegicus GN = Dlgap1 PE = 2 SV = 1 Ptges3 protein OS = Rattus norvegicus GN = Ptges3 PE = 2 SV = 1 Septin-8 OS = Rattus norvegicus GN = Sept8 PE = 1 SV = 1 Solute carrier family 2, facilitated glucose transporter member 8 OS = Rattus norvegicus GN = Slc2a8 PE = 1 SV = 1 Mitogen-activated protein kinase 1 OS = Rattus norvegicus GN = Mapk1 PE = 4 SV = 1 Guanine nucleotide-binding protein subunit gamma (Fragment) OS = Rattus norvegicus GN = Gng10 PE = 2 SV = 1 Aminoacylase-1A OS = Rattus norvegicus GN = Acy1a PE = 1 SV = 1 Disks large homolog 1 OS = Rattus norvegicus GN = Dlg1 PE = 2 SV = 1 Histidine triad nucleotide binding protein 2 (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Hint2 PE = 4 SV = 1 Ferritin (Fragment) OS = Rattus norvegicus GN = Fth1 PE = 2 SV = 1 Glutamate receptor, metabotropic 5, isoform CRA_a OS = Rattus norvegicus GN = Grm5 PE = 2 SV = 1 Myosin phosphatase Rho-interacting protein OS = Rattus norvegicus GN = Mprip PE = 2 SV = 1

58

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

F8WFS9_RAT

OST48_RAT

THRB_RAT S4A4_RAT IDHP_RAT NUCB1_RAT D4A1C0_RAT Q5BJU0_RAT F1LNW6_RAT D4A315_RAT F1M9V7_RAT H1UBM5_RAT RS27A_RAT CAH2_RAT B1WC61_RAT D3ZX38_RAT D4A772_RAT GNAZ_RAT F1LM82_RAT DYL1_RAT DYL2_RAT D3ZG43_RAT

D4A3V2_RAT

CSK21_RAT CYC_RAT KCNA1_RAT

8.3

19529.44

6.95

0

0.043

0.578987

0.144356

0.83143

0.370277

0.392995

0.045204

0.653078

0.117888

1

1

4.6

37598.49

6.08

0

0.527

0.629349

0.195906

0.703732

0.116013

1.18789

0.678075

1.3816

0.170631

2

2

7.3

34961.73

8.11

0

0.028

0.60986

0.174554

1.11879

0.590782

0.542419

0.12393

1.06414

0.822653

2

2

3.9

48895.09

5.62

2

0.003

0.626162

0.19229

1.16103

0.465326

0.811495

0.482396

1.45324

0.10336

1

1

1.9

70411.04

6.28

0

0.54

0.71562

0.313381

3.04131

1.48E20

2.88079

3.58E-07

5

5

5.7

6.44

0

0.006

0.638323

0.206359

0.676671

0.086357

0.623266

0.197994

0.712432

0.194374

2

1

2.9

50966.71

8.88

0

0.408

0.562136

0.129657

0.601789

0.034754

0.969398

0.83223

0.957331

0.841162

2

1

3.5

44373.13

5.09

0

1.031

0.478595

0.0732

0.737266

0.163237

0.638465

0.214952

0.816312

0.405249

2

1

1.1

6.1

0

0.203

0.790632

0.447125

0.961706

0.836373

0.62046

0.194973

0.792874

0.3486

2

2

17.9

20388.88

5.33

0

0.672

0.790424

0.446713

0.848391

0.420127

0.735887

0.348568

0.902467

0.65542

2

2

11.3

16834.43

8.68

0

0.246

0.688752

0.272659

0.668657

0.078859

0.663227

0.244778

0.702661

0.179748

3

2

11.5

17668.48

8.8

0

0.681697

0.262596

1.03692

0.869108

1.13923

0.778919

1.80333

0.00382

116040.2

103683

0.09

14.2467

0

8

5

6.5

103343.2

5.53

0

0.199

0.562195

0.129706

0.893617

0.570807

0.810775

0.481003

0.791205

0.344768

1

1

1.8

61188.6

5.5

0

0.304

0.671477

0.248477

1.54918

0.01249

0.774382

0.413493

1.7816

0.00489

13

6

46.8

17950.69

9.68

0

0.858

0.59449

0.158978

0.990021

0.95479

0.595094

0.169188

0.958207

0.844232

5

4

23.9

29113.45

6.89

0

0.526

0.656812

0.229159

0.83633

0.384288

0.605875

0.179816

1.23758

0.395191

6

5

8.0

68842.46

7.59

0

0.052

0.522388

0.099592

0.812732

0.319783

0.818978

0.49701

0.995195

0.975471

1

1

8.2

14255.36

6.32

0

0.642

0.677156

0.256256

0.855317

0.441569

0.556331

0.134847

0.757291

0.272752

1

1

1.2

84168.5

6.45

0

0.506

0.787341

0.44065

0.884468

0.538371

0.663636

0.245293

0.938339

0.775254

7

4

14.9

40879.23

7.53

0

0.376

0.643399

0.212448

0.937056

0.736129

0.709172

0.307551

1.02641

0.929941

1

1

4.8

33778.61

9.16

0

0.91

0.858461

0.59194

1.624

0.004529

0.353287

0.033493

1.08984

0.751311

4

2

20.2

10365.77

6.89

0

0.448

0.59511

0.159584

0.758276

0.199463

0.779089

0.421894

0.956897

0.839641

5

3

21.4

10349.73

6.81

0

0.456

0.619621

0.18502

0.830055

0.366403

0.736506

0.349559

1.06141

0.83033

7

6

15.2

30226.07

7.06

0

0.325

0.648918

0.219214

1.36226

0.099632

0.4353

0.061303

0.981837

0.927808

12

5

37.7

15223.58

10.15

0

0.54

0.624699

0.190646

1.26792

0.223632

0.701703

0.296679

1.35445

0.203322

10

8

20.7

36611.95

5.7

0

0.039

0.61726

0.182447

0.719296

0.136391

0.724024

0.329944

0.802682

0.371665

3

2

8.4

45072.94

7.29

0

0.452

0.560992

0.128702

1.28725

0.1919

0.434173

0.060819

1.13476

0.631901

25

6

41.0

11605.31

9.61

0

0.757

0.631494

0.198369

1.30667

0.16349

0.720896

0.325142

1.53847

0.052809

7

4

9.7

56378.75

5.04

4

0.067

0.626478

0.192646

0.900394

0.59542

0.653326

0.232521

0.918921

0.709508

59

(continued on next page)

No. of Pages 73

LDHB_RAT

1

NSC 16186

D3ZLK9_RAT

1

22 April 2015

AIP_RAT

Peptidyl-tRNA hydrolase 2 OS = Rattus norvegicus GN = Ptrh2 PE = 1 SV = 1 AH receptor-interacting protein OS = Rattus norvegicus GN = Aip PE = 1 SV = 1 ATP-dependent (S)-NAD(P)H-hydrate dehydratase OS = Rattus norvegicus GN = Carkd PE = 3 SV = 1 Dolichyl-diphosphooligosaccharide–protein glycosyltransferase 48 kDa subunit OS = Rattus norvegicus GN = Ddost PE = 2 SV = 1 Prothrombin OS = Rattus norvegicus GN = F2 PE = 1 SV = 1 Isoform 2 of Electrogenic sodium bicarbonate cotransporter 1 OS = Rattus norvegicus GN = Slc4a4 Isocitrate dehydrogenase [NADP], mitochondrial OS = Rattus norvegicus GN = Idh2 PE = 1 SV = 2 Nucleobindin-1 OS = Rattus norvegicus GN = Nucb1 PE = 4 SV = 1 Protein Cnnm1 OS = Rattus norvegicus GN = Cnnm1 PE = 4 SV = 1 Protein Rras2 (Fragment) OS = Rattus norvegicus GN = Rras2 PE = 2 SV = 1 Protein Ly6h (Fragment) OS = Rattus norvegicus GN = Ly6h PE = 2 SV = 1 Protein LOC680058 OS = Rattus norvegicus GN = LOC680058 PE = 4 SV = 1 Protein Npepps OS = Rattus norvegicus GN = Npepps PE = 2 SV = 1 Copine 6 protein OS = Rattus norvegicus GN = Cpne6 PE = 2 SV = 1 Ubiquitin-40S ribosomal protein S27a OS = Rattus norvegicus GN = Rps27a PE = 1 SV = 2 Carbonic anhydrase 2 OS = Rattus norvegicus GN = Ca2 PE = 1 SV = 2 Acad9 protein OS = Rattus norvegicus GN = Acad9 PE = 2 SV = 1 Prefoldin 1 (Predicted) OS = Rattus norvegicus GN = Pfdn1 PE = 4 SV = 1 Protein Dtna OS = Rattus norvegicus GN = Dtna PE = 2 SV = 1 Guanine nucleotide-binding protein G(z) subunit alpha OS = Rattus norvegicus GN = Gnaz PE = 2 SV = 3 Heterogeneous nuclear ribonucleoproteins A2/B1 (Fragment) OS = Rattus norvegicus GN = Hnrnpa2b1 PE = 2 SV = 1 Dynein light chain 1, cytoplasmic OS = Rattus norvegicus GN = Dynll1 PE = 1 SV = 1 Dynein light chain 2, cytoplasmic OS = Rattus norvegicus GN = Dynll2 PE = 1 SV = 1 NADH dehydrogenase (Ubiquinone) Fe-S protein 3 (Predicted), isoform CRA_c OS = Rattus norvegicus GN = Ndufs3 PE = 3 SV = 1 NADH dehydrogenase (Ubiquinone) 1 alpha subcomplex, 6 (B14) (Predicted) OS = Rattus norvegicus GN = Ndufa6 PE = 4 SV = 1 L-lactate dehydrogenase B chain OS = Rattus norvegicus GN = Ldhb PE = 1 SV = 2 Casein kinase II subunit alpha OS = Rattus norvegicus GN = Csnk2a1 PE = 1 SV = 2 Cytochrome c, somatic OS = Rattus norvegicus GN = Cycs PE = 1 SV = 2 Potassium voltage-gated channel subfamily A member 1 OS = Rattus norvegicus GN = Kcna1 PE = 1 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

Q5XI86_RAT

GSTM4_RAT ATPK_RAT F1M3P6_RAT GRM3_RAT ENPP6_RAT

F1LNT1_RAT D4A441_RAT

PROF2_RAT Q45QK6_RAT

D3ZFY8_RAT D3ZP34_RAT PLMN_RAT Q331S7_RAT F1LQ75_RAT D3ZTN1_RAT Q5U2P5_RAT RS13_RAT F1M6C4_RAT B4F7C8_RAT ASGL1_RAT S100B_RAT B0BNJ4_RAT

D3ZVW0_RAT Q5U3Z7_RAT

16837.42

4.09

0

0.654

0.547091

0.117539

0.816822

0.330423

0.521163

0.108598

0.812106

0.394696

4

2

34.8

10375.83

6.71

0

0.582

0.593623

0.158131

0.884565

0.538709

0.575472

0.151063

0.865221

0.539787

2

2

1.0

231941.6

6.57

0

0.149

0.571896

0.138021

1.16621

0.451036

0.91031

0.692526

1.39165

0.159596

8

5

21.6

25680.4

6.84

0

0.399

0.57198

0.138096

0.90767

0.622371

0.699905

0.294101

1.01452

0.964125

1

1

14.8

10452.24

10.05

0

0.348

0.656617

0.228909

1.81412

0.000212

0.562779

0.140152

1.759

0.006284

1

1

1.7

66647.21

6.7

0

0.451

0.726288

0.330606

1.05589

0.801644

0.524553

0.110938

0.877494

0.576748

2

1

1.3

96502.6

8.16

6

0.016

0.545992

0.11669

0.863325

0.467122

0.580108

0.155206

0.852776

0.503562

2

1

2.3

50700.76

6.47

0

0.188

0.575202

0.140948

1.02766

0.902402

0.653268

0.23245

1.06337

0.824832

3

3

1.6

5.75

0

0.304

0.668794

0.244859

1.00455

0.986137

0.718673

0.321757

1.13636

0.627782

10

3

9.3

37455.38

9.51

0

0.624808

0.190768

1.00313

0.991298

0.71731

0.319693

1.22262

0.42589

3

2

10.3

24603.64

10.11

0

0.553

0.579803

0.145099

1.3234

0.141667

0.492198

0.090166

0.828408

0.43652

8

5

28.6

15001.98

6.55

0

0.046

0.642651

0.211543

0.893578

0.570668

0.94407

0.771405

1.20816

0.456862

15

2

62.8

5667.56

5.66

0

0.069

0.60734

0.171924

0.862772

0.465331

0.539399

0.121655

0.838529

0.463719

2

1

6.8

16354.56

7.75

0

0.47

0.629351

0.195909

0.909335

0.628609

0.794517

0.450127

1.10463

0.711172

2

2

2.4

6.19

0

0.495

0.948021

0.810325

1.01688

0.941378

0.706213

0.303213

0.962702

0.860024

1

1

1.1

90534.82

6.79

0

0.697

0.394336

0.038445

1.52146

0.017706

0.769194

0.404347

1.87659

0.001594

1

1

12.0

17186.39

4.13

0

0.789

0.51788

0.096566

0.637467

0.054555

1.79916

0.035449

1.42996

0.122411

1

1

1.3

8.79

0

0.441

0.527874

0.103376

0.775734

0.233773

0.849294

0.558541

1.22961

0.411375

1

1

7.5

24599.42

4.89

0

0.514

0.796221

0.458242

0.809394

0.311267

0.417347

0.053969

0.766892

0.29201

1

1

3.0

60529.46

6.45

1

0.436

0.834436

0.538267

0.825995

0.355114

0.437774

0.062375

0.791527

0.345506

1

1

8.6

17222.08

10.53

0

0.454

0.483423

0.075795

0.891385

0.562808

0.53697

0.119848

0.943753

0.793899

1

1

6.4

20942.69

5.84

0

0.279

0.624595

0.19053

0.987049

0.942266

0.735826

0.348471

1.38555

0.16623

3

2

5.9

41530.99

9.47

1

0.154

0.395696

0.038868

0.817397

0.331939

0.981678

0.862111

0.870023

0.554108

1

1

3.0

34410.03

8.04

0

0.095

0.616593

0.181725

1.07912

0.721067

0.512122

0.10255

0.927772

0.739242

1

1

16.3

10743.94

4.52

0

0.517

0.835142

0.539809

1.17921

0.416269

0.775317

0.415153

1.16621

0.553462

3

2

13.4

27676.38

6.58

0

0.102

0.661053

0.234632

1.09327

0.673415

1.15112

0.753868

1.51999

0.061515

5

3

15.3

25202.61

7.8

0

0.318

0.55161

0.121082

0.739874

0.167443

1.00608

0.922025

1.08047

0.777121

1

1

9.6

12794.62

8.93

0

0.23

0.526

0.102071

0.516408

0.010376

0.750585

0.372552

0.750655

0.259963

2

2

4.4

55764.07

8.46

0

0.265

0.688204

0.271868

0.831942

0.371725

0.579454

0.154617

0.891014

0.618793

310776.1

127330.5

117219.6

No. of Pages 73

KAD4_RAT

32.2

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

RL10_RAT

6

NSC 16186

PI4KA_RAT

12

22 April 2015

TIM9_RAT

Calmodulin OS = Rattus norvegicus GN = Calm1 PE = 1 SV = 2 Mitochondrial import inner membrane translocase subunit Tim9 OS = Rattus norvegicus GN = Timm9 PE = 1 SV = 3 Protein Pi4ka OS = Rattus norvegicus GN = Pi4ka PE = 2 SV = 1 Glutathione S-transferase Yb-3 OS = Rattus norvegicus GN = Gstm3 PE = 1 SV = 2 ATP synthase subunit f, mitochondrial OS = Rattus norvegicus GN = Atp5j2 PE = 1 SV = 1 Protein Scai OS = Rattus norvegicus GN = Scai PE = 4 SV = 1 Metabotropic glutamate receptor 3 OS = Rattus norvegicus GN = Grm3 PE = 3 SV = 1 Ectonucleotide pyrophosphatase/phosphodiesterase family member 6 OS = Rattus norvegicus GN = Enpp6 PE = 2 SV = 1 Inositol 1,4,5-trisphosphate receptor type 1 OS = Rattus norvegicus GN = Itpr1 PE = 2 SV = 1 Uncharacterized protein OS = Rattus norvegicus PE = 4 SV = 1 60S ribosomal protein L10 OS = Rattus norvegicus GN = Rpl10 PE = 1 SV = 3 Profilin-2 OS = Rattus norvegicus GN = Pfn2 PE = 1 SV = 3 Guanine nucleotide-binding protein subunit gamma (Fragment) OS = Rattus norvegicus GN = Gng2 PE = 2 SV = 1 Protein Tmem189 OS = Rattus norvegicus GN = Tmem189 PE = 2 SV = 1 Protein Daam2 OS = Rattus norvegicus GN = Daam2 PE = 4 SV = 1 Plasminogen OS = Rattus norvegicus GN = Plg PE = 2 SV = 2 Protein Dbndd2 OS = Rattus norvegicus GN = Dbndd2 PE = 2 SV = 1 Protein Myo1g (Fragment) OS = Rattus norvegicus GN = Myo1g PE = 2 SV = 1 Protein Tesc OS = Rattus norvegicus GN = Tesc PE = 4 SV = 1 Protein C2cd2l OS = Rattus norvegicus GN = C2cd2l PE = 2 SV = 1 40S ribosomal protein S13 OS = Rattus norvegicus GN = Rps13 PE = 1 SV = 2 Protein Arl15 (Fragment) OS = Rattus norvegicus GN = Arl15 PE = 4 SV = 1 Agpat5 protein OS = Rattus norvegicus GN = Agpat5 PE = 2 SV = 1 Isoaspartyl peptidase/L-asparaginase OS = Rattus norvegicus GN = Asrgl1 PE = 1 SV = 1 Protein S100-B OS = Rattus norvegicus GN = S100b PE = 1 SV = 2 Ethylmalonic encephalopathy 1 OS = Rattus norvegicus GN = Ethe1 PE = 2 SV = 1 Adenylate kinase isoenzyme 4, mitochondrial OS = Rattus norvegicus GN = Ak4 PE = 2 SV = 1 Uncharacterized protein OS = Rattus norvegicus PE = 4 SV = 1 Serine hydroxymethyltransferase OS = Rattus norvegicus GN = Shmt2 PE = 2 SV = 1

60

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

CALM_RAT

D4A786_RAT GBRA1_RAT ACACA_RAT SYT1_RAT B5DFH0_RAT FUMH_RAT SPRY4_RAT D3Z9I6_RAT

KIF5A_RAT D3Z9Z0_RAT GTR3_RAT F1M1J2_RAT TALDO_RAT LIN7C_RAT D3ZXF9_RAT GNA11_RAT TOM70_RAT CATD_RAT SV2B_RAT PRDX2_RAT Q4QQV4_RAT M0R6L3_RAT MLEC_RAT

ADA17_RAT D4A7Y1_RAT

3.6

30810.1

4.93

0

0.475

0.470641

0.069084

1.54067

0.013925

0.379079

0.040758

0.808311

0.385319

2

1

3.6

33965.11

4.99

0

0.322

0.594442

0.15893

0.582626

0.026924

0.672321

0.256429

0.726113

0.216292

6

4

24.2

23674.5

8.29

0

0.39

0.554657

0.123517

0.745304

0.176462

0.59692

0.170953

0.791

0.3443

4

2

27.6

6381.45

9.84

0

0.047

0.554392

0.123304

1.13631

0.536895

0.4303

0.059182

0.866496

0.543572

2

2

7.3

51753.08

9.34

4

0.234

0.55198

0.121375

0.729659

0.151423

0.606689

0.180638

0.616114

0.08375

2

2

1.1

269874.1

6.03

0

0.236

0.66473

0.239451

0.900714

0.596593

0.488021

0.087729

0.743489

0.246623

19

13

26.6

47398.4

8.57

0

0.416

0.554625

0.123491

0.763698

0.209699

0.622957

0.19766

0.875118

0.569501

1

1

2.3

45732.7

6.32

1

0.804

0.725602

0.329481

0.841352

0.398977

0.736058

0.348842

1.16387

0.559111

6

4

8.7

54463.27

9.06

0

0.09

0.564674

0.131793

0.99233

0.964525

0.946753

0.77779

1.34954

0.209683

1

1

4.8

23249.38

9.39

0

0.233

0.631728

0.19864

0.666721

0.07713

1.00775

0.926154

1.40526

0.14551

1

1

3.8

42435.16

5.24

0

0.446545

0.05776

1.4339

0.048503

0.440684

0.063656

1.13761

0.62459

1

1

1.2

116914.2

5.56

0

0.752

0.598834

0.163269

0.819985

0.338808

0.592435

0.16664

0.828242

0.43608

17

9

5.2

206716.5

6.1

0

0.376

0.575941

0.141608

0.850406

0.426302

0.710439

0.309421

0.954085

0.829802

1

1

1.8

4.95

6

0.63

0.700305

0.289703

0.78685

0.257688

0.703609

0.299429

0.709716

0.190223

2

2

0.5

9.13

0

0.816

0.515531

0.095018

0.920688

0.671853

0.635438

0.211494

1.00897

0.980095

1

1

2.7

37459.64

6.57

0

0.275

0.571018

0.137253

1.02027

0.929108

0.715935

0.31762

1.3288

0.238176

4

2

11.7

21833.72

8.52

0

0.447

0.530699

0.105369

0.789032

0.262576

1.12023

0.819458

1.04965

0.863588

1

1

4.0

29441.09

9.7

0

0.162

0.608301

0.172923

1.05322

0.811054

0.460091

0.072769

0.817777

0.408962

9

2

5.0

42025.66

5.91

0

0.351

0.557125

0.125517

0.873073

0.499306

0.995737

0.896562

1.63897

0.021489

15

11

16.4

67444.26

7.44

0

0.498

0.525561

0.101767

0.953603

0.803038

0.606454

0.1804

0.967852

0.878187

5

3

9.8

44680.18

6.66

1

0.008

0.634634

0.202014

1.20136

0.360829

0.657579

0.237732

1.30685

0.271188

7

4

5.1

77459.52

5.4

12

0.079

0.590104

0.154731

0.772392

0.226901

0.81009

0.47968

1.11694

0.678347

8

4

22.2

21783.41

5.34

0

0.164

0.487014

0.077773

0.845237

0.410571

0.783997

0.43076

1.08146

0.774378

2

2

4.9

57359.55

5.86

0

0.309

0.416308

0.045775

0.851497

0.429668

0.402199

0.048365

0.66055

0.125962

1

1

6.2

17163.85

0

1.135

0.9525

0.821821

1.16312

0.459548

0.570062

0.146336

1.47088

0.090553

2

2

6.9

32417.71

5.38

1

0.22

0.529393

0.104444

0.771275

0.224636

0.697752

0.291034

0.976337

0.908248

23

11

24.8

49489.18

5.72

0

0.827

0.502006

0.086491

0.744642

0.175342

0.681655

0.268782

0.838217

0.462868

1

1

1.2

73637.38

5.89

1

0.532

0.509367

0.091052

0.894981

0.575723

0.46593

0.07571

0.61715

0.084584

2

2

1.0

4.16

0

0.377

0.506556

0.089288

0.553736

0.018006

0.580784

0.155817

0.553109

0.044258

53580.24 425878.9

223896

10.6

61

(continued on next page)

No. of Pages 73

GFAP_RAT

1

NSC 16186

A1L1J8_RAT

1

22 April 2015

O70371_RAT

Acyl-CoA-binding domain-containing protein 6 OS = Rattus norvegicus GN = Acbd6 PE = 2 SV = 1 Annexin (Fragment) OS = Rattus norvegicus GN = Anxa5 PE = 2 SV = 1 Protein Rab5b OS = Rattus norvegicus GN = Rab5b PE = 2 SV = 1 Protein LOC100364994 OS = Rattus norvegicus GN = LOC100362685 PE = 4 SV = 1 Gamma-aminobutyric acid receptor subunit alpha-1 OS = Rattus norvegicus GN = Gabra1 PE = 1 SV = 1 Acetyl-CoA carboxylase 1 OS = Rattus norvegicus GN = Acaca PE = 2 SV = 1 Synaptotagmin-1 OS = Rattus norvegicus GN = Syt1 PE = 1 SV = 3 Downstream of Stk11 OS = Rattus norvegicus GN = Dos PE = 2 SV = 1 Fumarate hydratase, mitochondrial OS = Rattus norvegicus GN = Fh PE = 1 SV = 1 SPRY domain-containing protein 4 OS = Rattus norvegicus GN = Spryd4 PE = 2 SV = 1 Heterogeneous nuclear ribonucleoproteins methyltransferase-like 2 (S. cerevisiae), isoform CRA_b OS = Rattus norvegicus GN = LOC100361025 PE = 4 SV = 1 Kinesin heavy chain isoform 5A OS = Rattus norvegicus GN = Kif5a PE = 1 SV = 1 Protein Ank1 OS = Rattus norvegicus GN = Ank1 PE = 2 SV = 1 Solute carrier family 2, facilitated glucose transporter member 3 OS = Rattus norvegicus GN = Slc2a3 PE = 1 SV = 1 Protein Neb (Fragment) OS = Rattus norvegicus GN = Neb PE = 2 SV = 1 Transaldolase OS = Rattus norvegicus GN = Taldo1 PE = 1 SV = 2 Protein lin-7 homolog C OS = Rattus norvegicus GN = Lin7c PE = 1 SV = 1 Protein Mrpl12 OS = Rattus norvegicus GN = Mrpl12 PE = 4 SV = 1 Guanine nucleotide-binding protein subunit alpha-11 OS = Rattus norvegicus GN = Gna11 PE = 2 SV = 1 Mitochondrial import receptor subunit TOM70 OS = Rattus norvegicus GN = Tomm70a PE = 1 SV = 1 Cathepsin D OS = Rattus norvegicus GN = Ctsd PE = 1 SV = 1 Synaptic vesicle glycoprotein 2B OS = Rattus norvegicus GN = Sv2b PE = 4 SV = 1 Peroxiredoxin-2 OS = Rattus norvegicus GN = Prdx2 PE = 1 SV = 3 Dead end homolog 1 (Zebrafish) OS = Rattus norvegicus GN = Hars PE = 2 SV = 1 Uncharacterized protein OS = Rattus norvegicus GN = LOC100910721 PE = 3 SV = 1 Malectin OS = Rattus norvegicus GN = Mlec PE = 2 SV = 1 Glial fibrillary acidic protein OS = Rattus norvegicus GN = Gfap PE = 3 SV = 1 Disintegrin and metalloproteinase domain-containing protein 17 OS = Rattus norvegicus GN = Adam17 PE = 2 SV = 1 Aggrecan core protein OS = Rattus norvegicus GN = Acan PE = 2 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

ACBD6_RAT

RAB15_RAT PPID_RAT Q5U1W6_RAT SGTA_RAT

OCAD1_RAT BPNT1_RAT SAP_RAT

MFR1L_RAT Q6P9W6_RAT LPHN3_RAT F1LZ53_RAT PITM1_RAT GLSK_RAT PCCB_RAT C9WPN2_RAT PAFA2_RAT F1LP82_RAT Q924Y3_RAT G3V7I0_RAT D3ZT36_RAT Q566E4_RAT D3ZYM7_RAT

MK10_RAT O35357_RAT

87328.41

7.2

0

0.09

0.633584

0.20079

0.737252

0.163214

0.511914

0.102413

0.772214

0.303067

2

2

6.4

37554.15

6.53

0

0.382

0.523745

0.100517

0.619142

0.043448

0.656172

0.235998

0.844948

0.481449

1

1

2.9

46568.11

6.47

0

0.219

0.524147

0.100793

0.802337

0.293756

0.708256

0.306203

1.13107

0.641392

6

2

9.9

24283.15

5.36

0

0.534

0.576707

0.142295

0.805527

0.301588

1.20478

0.644256

2.17955

2.13E05

2

2

4.9

40765.22

6.73

0

0.421

0.41661

0.045884

0.851746

0.430437

0.636291

0.212464

0.86062

0.526243

2

2

14.4

23890.31

9.03

0

0.407

0.578019

0.143478

0.839137

0.392456

0.595871

0.169937

0.81554

0.403298

1

1

4.1

34284.92

5.05

0

0.5

0.486695

0.077596

1.01776

0.938199

0.713581

0.314091

1.54994

0.047941

1

1

3.2

27658.77

6.97

0

0.753

0.572082

0.138185

0.938663

0.742549

0.555162

0.133902

0.98551

0.940894

2

1

6.0

28968.76

5.59

0

0.052

0.720132

0.320593

1.04534

0.838999

0.355432

0.034052

0.645983

0.110602

6

3

5.8

61123.4

5.13

0

0.034

0.526148

0.102174

1.06383

0.773811

0.574728

0.150407

1.15111

0.590516

4

4

10.0

34346.63

6.84

0

0.44

0.499616

0.085051

0.766597

0.215326

0.684022

0.271979

0.945878

0.801251

2

1

4.2

31729.8

5.77

0

0.289

0.503946

0.087675

0.948447

0.782007

0.422642

0.056052

0.827728

0.434724

10

3

14.9

25913.9

5.03

0

0.346

0.532013

0.106305

0.678564

0.08821

0.694299

0.286159

0.885759

0.60229

1

1

0.7

144890.6

7.32

0

0.199

0.665002

0.239811

0.896943

0.582825

0.670561

0.254144

1.0824

0.771773

1

1

15.0

9.61

0

0.483

0.984861

0.905878

0.737812

0.16411

0.562374

0.139815

0.693617

0.166955

3

2

2.6

134982.4

5.64

0

0.306

0.647866

0.217913

0.876333

0.510328

0.616964

0.191257

1.3493

0.209998

21

12

23.2

74022.9

8.06

0

0.29

0.51301

0.09338

0.791389

0.267926

0.564937

0.141964

0.899846

0.646963

4

2

4.6

54981.3

8.26

0

0.022

0.553039

0.122219

0.827511

0.359304

0.502927

0.096676

0.915344

0.697613

4

3

6.8

73005.64

6.67

0

0.666

0.396328

0.039065

0.766073

0.214301

0.608784

0.182766

1.10313

0.715195

1

1

2.6

43491.42

6.23

0

0.074

1.01355

0.981305

1.33921

0.123158

0.715999

0.317717

0.575948

0.056223

26

7

36.8

23517.23

6.08

0

0.46

0.479803

0.073842

0.673094

0.082942

0.781519

0.426271

1.29679

0.287331

4

2

14.4

12040.45

8.62

4

0.777

0.468573

0.068045

0.331074

0.000394

0.508366

0.100117

0.377782

0.005154

4

3

12.8

28299.03

7.14

0

0.03

0.410954

0.043888

0.831115

0.369387

0.864756

0.591289

1.24765

0.375297

4

3

6.0

91608.62

6.95

0

0.469

0.431641

0.051561

0.50061

0.008129

0.620363

0.19487

0.846185

0.484907

1

1

1.7

70873.17

8.23

0

0.934

0.415975

0.045656

0.649557

0.063109

0.406139

0.049773

0.69643

0.170858

1

1

7.7

10816.37

10.06

0

0.664

0.501281

0.086052

1.03917

0.861048

0.543687

0.124896

1.21552

0.440942

1

1

0.7

6.12

0

0.561

0.567451

0.134161

0.772592

0.227307

0.402423

0.048444

0.515183

0.029141

1

1

3.2

52529.78

6.37

0

0.294

0.423933

0.048581

0.874218

0.503163

0.479742

0.083056

0.664381

0.130266

3

1

47.2

3992.52

5.56

0

0.103

0.421709

0.047748

0.48117

0.005968

0.597945

0.171951

0.600611

0.072051

9470.79

120570.3

No. of Pages 73

Q99PW9_RAT

1.4

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

ARPC2_RAT

1

NSC 16186

D3ZUZ4_RAT

1

22 April 2015

PHYIP_RAT

Protein Aldh18a1 OS = Rattus norvegicus GN = Aldh18a1 PE = 4 SV = 1 Phytanoyl-CoA hydroxylase-interacting protein OS = Rattus norvegicus GN = Phyhip PE = 2 SV = 1 Protein Fam20b OS = Rattus norvegicus GN = Fam20b PE = 4 SV = 1 Ras-related protein Rab-15 OS = Rattus norvegicus GN = Rab15 PE = 2 SV = 1 Peptidyl-prolyl cis-trans isomerase D OS = Rattus norvegicus GN = Ppid PE = 1 SV = 3 Protein Apool OS = Rattus norvegicus GN = Apool PE = 2 SV = 1 Small glutamine-rich tetratricopeptide repeat-containing protein alpha OS = Rattus norvegicus GN = Sgta PE = 2 SV = 1 OCIA domain-containing protein 1 OS = Rattus norvegicus GN = Ociad1 PE = 2 SV = 1 3’(2’),5’-bisphosphate nucleotidase 1 (Fragment) OS = Rattus norvegicus GN = Bpnt1 PE = 2 SV = 1 Sulfated glycoprotein 1 OS = Rattus norvegicus GN = Psap PE = 1 SV = 1 Actin related protein 2/3 complex, subunit 2 (Predicted), isoform CRA_a OS = Rattus norvegicus GN = Arpc2 PE = 4 SV = 1 Mitochondrial fission regulator 1-like OS = Rattus norvegicus GN = Mtfr1l PE = 2 SV = 1 Rab3b protein OS = Rattus norvegicus GN = Rab3b PE = 2 SV = 1 Isoform 4 of Latrophilin-3 OS = Rattus norvegicus GN = Lphn3 Protein Exoc6b (Fragment) OS = Rattus norvegicus GN = Exoc6b PE = 4 SV = 1 Membrane-associated phosphatidylinositol transfer protein 1 OS = Rattus norvegicus GN = Pitpnm1 PE = 2 SV = 1 Glutaminase kidney isoform, mitochondrial OS = Rattus norvegicus GN = Gls PE = 1 SV = 2 Propionyl-CoA carboxylase beta chain, mitochondrial OS = Rattus norvegicus GN = Pccb PE = 2 SV = 1 DEAD (Asp-Glu-Ala-Asp) box polypeptide 3 Y-linked OS = Rattus norvegicus GN = Ddx3y PE = 2 SV = 1 Platelet-activating factor acetylhydrolase 2, cytoplasmic OS = Rattus norvegicus GN = Pafah2 PE = 1 SV = 2 Ras-related protein Rab-2A OS = Rattus norvegicus GN = Rab2a PE = 2 SV = 1 Claudin 11 (Fragment) OS = Rattus norvegicus GN = Cldn11 PE = 2 SV = 1 Peroxiredoxin 3 OS = Rattus norvegicus GN = Prdx3 PE = 4 SV = 1 Protein Adam23 OS = Rattus norvegicus GN = Adam23 PE = 2 SV = 1 Heterogeneous nuclear ribonucleoprotein R OS = Rattus norvegicus GN = Hnrnpr PE = 2 SV = 1 Protein LOC100363003 OS = Rattus norvegicus GN = Lyrm4 PE = 4 SV = 1 Huntingtin interacting protein 1 related (Fragment) OS = Rattus norvegicus GN = Hip1r PE = 2 SV = 1 Mitogen-activated protein kinase 10 OS = Rattus norvegicus GN = Mapk10 PE = 1 SV = 2 Guanine nucleotide-binding protein subunit gamma (Fragment) OS = Rattus norvegicus GN = Gng4 PE = 2 SV = 1

62

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

D3ZIE9_RAT

NEB1_RAT Q6P9U5_RAT B5DEP0_RAT MOSC2_RAT PSA6_RAT LRRT1_RAT A1L1L6_RAT RLA2_RAT G3V7L6_RAT D3ZZ32_RAT Q4G022_RAT RL10A_RAT IVD_RAT LACB2_RAT F1LSL8_RAT F1LUA1_RAT B1WBY5_RAT F1LN88_RAT PRDX6_RAT NCPR_RAT CREL1_RAT F210A_RAT GLRX2_RAT B5DEP1_RAT

VATF_RAT D4ABK1_RAT

44.7

30928.66

8.91

0

0.289

0.50663

0.089334

0.911423

0.636474

0.556573

0.135044

1.06081

0.83203

1

1

1.9

46183.08

7.59

0

0.204

0.580583

0.145812

0.82318

0.347417

0.554828

0.133633

0.960006

0.850544

1

1

1.1

70189.87

7.83

6

0.099

0.516757

0.095823

0.656828

0.068767

0.59837

0.172366

0.79674

0.357581

1

1

0.9

5.05

0

1.011

0.509173

0.09093

1.0122

0.958346

0.446729

0.066388

0.799854

0.36492

1

1

5.2

21921.19

0

0.37

0.474198

0.0709

0.881134

0.526785

0.519207

0.107266

1.14939

0.594806

1

1

4.4

21469.18

5.65

0

0.436

0.533351

0.107267

1.02475

0.912913

0.513674

0.103569

1.05805

0.839803

3

2

4.1

38248.09

8.95

1

0.21

0.581289

0.146459

0.964422

0.847615

0.62255

0.19722

1.33867

0.2243

1

1

3.7

27399.16

6.35

0

0.178

0.589247

0.153912

0.924496

0.686618

0.767756

0.401833

1.53888

0.052628

1

1

1.5

58731.07

6.65

0

0.021

0.513686

0.093817

0.79079

0.26656

0.474997

0.08047

1.0031

0.997007

5

5

8.0

80693.78

6.57

1

0.276

0.435214

0.052994

0.863621

0.468083

0.819039

0.497129

1.07499

0.792317

2

2

20.9

11691.82

4.44

0

0.263

0.411142

0.043954

0.769667

0.221405

0.356717

0.03439

0.687402

0.158568

1

1

3.2

48633.3

5.71

0

0.416

0.45868

0.063253

0.79538

0.277156

0.527315

0.112873

0.931713

0.752611

122733.9

10

1

1

1.2

83338.33

5.84

0

0.467

0.368104

0.031023

0.754226

0.192058

0.332795

0.028539

0.662629

0.128283

3

1

2.7

36946.44

5.02

0

0.111

0.50337

0.087322

0.869083

0.485992

0.294263

0.020915

0.731683

0.225709

2

2

13.4

24831.02

9.94

0

0.408

0.45774

0.062813

0.89879

0.589551

0.691838

0.282719

1.32138

0.249002

4

3

10.4

46434.95

8.03

0

0.113

0.444727

0.056972

0.996148

0.980638

0.589234

0.163612

1.46927

0.091672

1

1

3.8

32483.76

5.9

0

0.315

0.625434

0.19147

1.0098

0.96706

0.652646

0.231696

1.10083

0.721425

3

3

1.4

5.73

0

0.593

0.35701

0.028275

0.551284

0.017384

0.550461

0.130153

0.628846

0.094469

1

1

1.4

97195.36

5.29

0

1.01

0.635947

0.203553

0.879547

0.521313

0.508506

0.100207

1.25729

0.35684

2

2

5.4

63204.32

8.5

0

0.403

0.809432

0.485128

0.814454

0.324236

1.15405

0.747725

1.43403

0.118896

7

5

9.3

56310.47

6.99

0

0.14

0.461481

0.064581

0.924136

0.685216

0.425625

0.057254

1.20217

0.470032

3

3

16.5

24818.28

5.64

0

0.215

0.469145

0.068331

1.62084

0.004737

0.643402

0.220679

0.729614

0.222177

1

1

1.3

76961.98

5.3

1

0.433

0.415112

0.045348

1.24565

0.264638

0.495034

0.091852

1.56531

0.042018

2

1

2.6

45696.47

4.94

2

0.214

0.974729

0.879401

0.912639

0.641074

0.893367

0.654101

0.918798

0.709099

1

1

5.5

31473.98

9.82

1

0.541

0.51702

0.095997

1.10246

0.64314

0.492495

0.090341

1.21841

0.434781

1

1

7.6

17274.67

9.69

0

0.232

0.490234

0.079583

0.889123

0.554757

0.811993

0.483363

2.04215

0.000174

1

1

5.8

21700.03

5.36

0

0.435

0.529339

0.104406

0.679117

0.088757

0.550719

0.130357

1.05076

0.860442

2

1

7.8

16793.04

5.38

0

0.351

0.605136

0.169649

0.490147

0.006892

0.386981

0.043235

0.637147

0.102031

1

1

6.7

13370.11

5.52

0

0.258

0.559931

0.127822

0.672554

0.082436

0.417466

0.054015

0.712015

0.193732

1

1

9.6

21369.36

9.4

0

0.464

0.388065

0.036545

0.434951

0.002752

0.261073

0.015838

0.323844

0.002374

288312

63

(continued on next page)

No. of Pages 73

G3V7J7_RAT

13

NSC 16186

KCNC2_RAT

27

22 April 2015

R4RL2_RAT

Isoform 2 of Voltage-dependent anion-selective channel protein 3 OS = Rattus norvegicus GN = Vdac3 Reticulon-4 receptor-like 2 OS = Rattus norvegicus GN = Rtn4rl2 PE = 2 SV = 1 Potassium voltage-gated channel subfamily C member 2 OS = Rattus norvegicus GN = Kcnc2 PE = 1 SV = 1 Neurabin-1 OS = Rattus norvegicus GN = Ppp1r9a PE = 1 SV = 1 Ribosomal protein L9 OS = Rattus norvegicus GN = Rpl9 PE = 2 SV = 1 Dguok protein OS = Rattus norvegicus GN = Dguok PE = 2 SV = 1 MOSC domain-containing protein 2, mitochondrial OS = Rattus norvegicus GN = Marc2 PE = 2 SV = 1 Proteasome subunit alpha type-6 OS = Rattus norvegicus GN = Psma6 PE = 1 SV = 1 Leucine-rich repeat transmembrane neuronal protein 1 OS = Rattus norvegicus GN = Lrrtm1 PE = 3 SV = 1 Mitochondrial Rho GTPase OS = Rattus norvegicus GN = Rhot1 PE = 2 SV = 1 60S acidic ribosomal protein P2 OS = Rattus norvegicus GN = Rplp2 PE = 1 SV = 2 26S protease regulatory subunit 7 OS = Rattus norvegicus GN = Psmc2 PE = 3 SV = 1 Prolyl endopeptidase-like OS = Rattus norvegicus GN = Prepl PE = 2 SV = 1 Asna1 protein (Fragment) OS = Rattus norvegicus GN = Asna1 PE = 2 SV = 1 60S ribosomal protein L10a OS = Rattus norvegicus GN = Rpl10a PE = 1 SV = 2 Isovaleryl-CoA dehydrogenase, mitochondrial OS = Rattus norvegicus GN = Ivd PE = 1 SV = 2 Beta-lactamase-like protein 2 OS = Rattus norvegicus GN = Lactb2 PE = 2 SV = 1 Protein Sptbn4 OS = Rattus norvegicus GN = Sptbn4 PE = 2 SV = 1 Protein Eea1 (Fragment) OS = Rattus norvegicus GN = Eea1 PE = 2 SV = 1 DnaJ (Hsp40) homolog, subfamily C, member 11 OS = Rattus norvegicus GN = Dnajc11 PE = 2 SV = 1 Aldehyde dehydrogenase, mitochondrial OS = Rattus norvegicus GN = Aldh2 PE = 2 SV = 1 Peroxiredoxin-6 OS = Rattus norvegicus GN = Prdx6 PE = 1 SV = 3 NADPH–cytochrome P450 reductase OS = Rattus norvegicus GN = Por PE = 1 SV = 3 Cysteine-rich with EGF-like domain protein 1 OS = Rattus norvegicus GN = Creld1 PE = 2 SV = 1 Protein FAM210A OS = Rattus norvegicus GN = Fam210a PE = 2 SV = 1 Glutaredoxin-2, mitochondrial OS = Rattus norvegicus GN = Glrx2 PE = 2 SV = 2 Pdcd6 protein OS = Rattus norvegicus GN = Pdcd6 PE = 2 SV = 1 Eukaryotic translation initiation factor 5A2 (Predicted) OS = Rattus norvegicus GN = Eif5a2 PE = 4 SV = 1 V-type proton ATPase subunit F OS = Rattus norvegicus GN = Atp6v1f PE = 1 SV = 1 Protein Syngr3 OS = Rattus norvegicus GN = Syngr3 PE = 4 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

VDAC3_RAT

TCTP_RAT GBB3_RAT Q6P7A8_RAT AMPH_RAT SYDC_RAT D4A164_RAT D4A376_RAT

DLRB1_RAT CNRP1_RAT F1LN92_RAT Q7TP78_RAT NMDE1_RAT PPIB_RAT VP33B_RAT G3V8C3_RAT SYTM_RAT ANXA6_RAT CX7A2_RAT Q4V8I9_RAT PP1A_RAT

SYRC_RAT RM37_RAT D3Z912_RAT

OTUB1_RAT F1M027_RAT SYJ2B_RAT

94661.24

6.04

0

0.173

0.504559

0.088052

0.963055

0.841953

0.294368

0.020933

0.671419

0.138468

5

3

15.1

25178.31

8.24

0

0.309

0.352696

0.027264

0.59191

0.030503

0.770283

0.406256

1.27747

0.320094

2

2

1.7

6.96

0

0.098

0.492757

0.081024

1.18493

0.401492

0.488245

0.087859

1.1413

0.615198

2

1

8.1

19461.97

4.76

0

0.361

0.409175

0.043276

0.674126

0.083916

0.283538

0.019138

0.588159

0.063655

9

3

8.5

37179.75

5.51

0

0.077

0.342908

0.025087

0.587079

0.028593

0.538834

0.121232

0.785498

0.331869

2

2

4.3

70610.9

4.56

0

1.061

0.981203

0.896304

1.58288

0.008015

0.464977

0.075224

1.1957

0.484514

1

1

1.6

74876.95

4.57

0

0.678

0.319219

0.02043

0.620549

0.044227

0.325115

0.026853

0.596624

0.069269

1

1

2.0

57125.57

6.02

0

0.395

0.379367

0.034044

0.333851

0.000417

1.09073

0.883304

1.16494

0.556522

2

2

1.8

8.19

0

1.026

0.38609

0.035964

0.3806

0.001032

0.941996

0.766481

0.876767

0.574525

2

2

21.4

16143.51

9.86

0

0.477

0.632731

0.1998

0.488488

0.006712

0.502376

0.096333

0.469181

0.016954

1

1

5.6

17017.5

5.82

0

0.052

0.338802

0.024219

0.519931

0.010947

0.406995

0.050084

0.592541

0.066513

1

1

20.4

11956.74

9.35

0

0.392

0.786587

0.439173

0.994384

0.97319

0.210357

0.010164

0.921888

0.719428

120634.6

116172.6

3

2

15.9

18987.71

9.45

0

0.341

0.373902

0.032548

0.633966

0.052267

0.386928

0.043218

0.912202

0.687225

6

4

5.5

89350.45

8.77

0

0.359

0.439416

0.054722

0.867479

0.480694

0.457607

0.071546

0.592553

0.06652

5

4

20.1

21966.06

8.39

0

0.581

0.348857

0.026392

0.825086

0.352616

0.358642

0.034903

1.01713

0.956601

2

2

2.0

165466.7

6.59

4

0.403

0.345537

0.025656

0.598308

0.033202

0.523543

0.110236

0.764273

0.286668

6

4

19.0

23802.3

9.5

1

0.202

0.338857

0.024231

0.608568

0.037956

0.368401

0.037602

1.10276

0.716197

1

1

1.5

70692.66

6.43

0

0.244

0.483251

0.075701

0.880798

0.525624

0.405824

0.049659

1.08929

0.75283

3 2

2 2

3.4 3.2

53700.03 81542.13

5.06 8.24

0 0

0.839 0.318

0.33738 0.266841

0.023925 0.012721

0.5967 1.69424

0.032505 0.001585

0.32481 0.324403

0.026787 0.026701

0.67227 1.74609

0.139486 0.007231

2

2

2.2

75753.3

5.39

0

0.432

0.236683

0.009565

0.862219

0.463545

0.312902

0.024348

1.07717

0.786269

9

2

18.1

9352.87

10.28

1

0.258

0.308413

0.018569

0.634825

0.052821

0.205817

0.009757

0.550054

0.042834

2

2

5.4

56220.79

7.8

0

0.289

0.924983

0.751887

0.87877

0.518648

0.653286

0.232472

1.07042

0.805067

6

4

13.3

37511.67

5.94

0

0.301

0.329001

0.022253

0.688096

0.098031

0.543782

0.124969

0.702694

0.179797

1

1

1.5

75809.54

6.65

0

0.336

0.606814

0.171379

0.945604

0.770479

0.326968

0.027251

1.05016

0.862141

1

1

2.1

48365.34

9.08

0

0.326

0.394579

0.03852

0.956365

0.814364

0.406934

0.050061

1.60725

0.028905

2

2

8.5

38831.88

6.99

0

0.368

0.324958

0.021483

0.52217

0.011324

0.446988

0.066507

1.38428

0.167637

2

2

2.6

58812.68

6.62

0

0.222

0.272637

0.013424

0.70968

0.123499

0.296006

0.021217

0.831101

0.443664

5

3

7.8

31269.66

4.85

0

0.553

0.405167

0.041923

0.77562

0.233535

0.388892

0.043853

0.922038

0.719933

1 2

1 1

4.0 8.3

46401.41 15824.72

6 6.27

0 1

0.466 0.137

1.47602 0.299718

0.244925 0.017181

0.645228 0.776883

0.059927 0.23617

0.273119 0.237574

0.017539 0.012932

0.311065 0.738629

0.00196 0.237854

No. of Pages 73

NLTP_RAT

1.2

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

AP2S1_RAT

1

NSC 16186

ACLY_RAT

1

22 April 2015

B0BNK1_RAT

Protein Slitrk6 OS = Rattus norvegicus GN = Slitrk6 PE = 4 SV = 1 Protein Rab5c OS = Rattus norvegicus GN = Rab5c PE = 2 SV = 1 ATP-citrate synthase OS = Rattus norvegicus GN = Acly PE = 1 SV = 1 Translationally-controlled tumor protein OS = Rattus norvegicus GN = Tpt1 PE = 1 SV = 1 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 OS = Rattus norvegicus GN = Gnb3 PE = 1 SV = 1 SPARC-like 1 (Hevin) OS = Rattus norvegicus GN = Sparcl1 PE = 2 SV = 1 Amphiphysin OS = Rattus norvegicus GN = Amph PE = 1 SV = 1 Aspartate–tRNA ligase, cytoplasmic OS = Rattus norvegicus GN = Dars PE = 2 SV = 1 Protein Nebl OS = Rattus norvegicus GN = Nebl PE = 4 SV = 1 Ras-related protein Rab-12 OS = Rattus norvegicus GN = Rab12 PE = 2 SV = 1 AP-2 complex subunit sigma OS = Rattus norvegicus GN = Ap2s1 PE = 2 SV = 1 Dynein light chain roadblock-type 1 (Fragment) OS = Rattus norvegicus GN = Dynlrb1 PE = 4 SV = 1 CB1 cannabinoid receptor-interacting protein 1 OS = Rattus norvegicus GN = Cnrip1 PE = 2 SV = 1 Protein Afg3l2 OS = Rattus norvegicus GN = Afg3l2 PE = 2 SV = 1 Aa2-258 OS = Rattus norvegicus GN = Ndufa8 PE = 2 SV = 1 Glutamate receptor ionotropic, NMDA 2A OS = Rattus norvegicus GN = Grin2a PE = 1 SV = 2 Peptidyl-prolyl cis-trans isomerase B OS = Rattus norvegicus GN = Ppib PE = 2 SV = 3 Vacuolar protein sorting-associated protein 33B OS = Rattus norvegicus GN = Vps33b PE = 2 SV = 1 Vimentin OS = Rattus norvegicus GN = Vim PE = 3 SV = 1 Threonine–tRNA ligase, mitochondrial OS = Rattus norvegicus GN = Tars2 PE = 2 SV = 1 Annexin A6 OS = Rattus norvegicus GN = Anxa6 PE = 1 SV = 2 Cytochrome c oxidase subunit 7A2, mitochondrial OS = Rattus norvegicus GN = Cox7a2 PE = 1 SV = 1 Protein Ugp2 (Fragment) OS = Rattus norvegicus GN = Ugp2 PE = 2 SV = 1 Serine/threonine-protein phosphatase PP1-alpha catalytic subunit OS = Rattus norvegicus GN = Ppp1ca PE = 1 SV = 1 Arginine–tRNA ligase, cytoplasmic OS = Rattus norvegicus GN = Rars PE = 1 SV = 2 39S ribosomal protein L37, mitochondrial OS = Rattus norvegicus GN = Mrpl37 PE = 2 SV = 1 Uncharacterized protein OS = Rattus norvegicus PE = 4 SV = 1 Non-specific lipid-transfer protein OS = Rattus norvegicus GN = Scp2 PE = 1 SV = 3 Ubiquitin thioesterase OTUB1 OS = Rattus norvegicus GN = Otub1 PE = 1 SV = 1 Chn3 OS = Rattus norvegicus GN = Chn3 PE = 2 SV = 1 Synaptojanin-2-binding protein OS = Rattus norvegicus GN = Synj2bp PE = 1 SV = 2

64

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

D3ZP44_RAT

Q6PCT9_RAT

B2RYF6_RAT B2GUZ9_RAT PRDX4_RAT D4A1W2_RAT D3ZBB7_RAT BI2L1_RAT

2ABA_RAT

2

7.8

24857.45

6.01

2

0.127

0.412416

0.044397

1.04983

0.823046

0.685581

0.274098

1.81596

0.003301

1

1

5.4

27351.8

9.7

1

0.113

0.261169

0.012065

1.47373

0.031216

0.224625

0.011541

1.43698

0.116392

1

1

1.4

67038.14

6.83

2

0.136

0.216878

0.007893

0.700124

0.111649

0.195124

0.008857

0.566685

0.05108

2

1

2.3

45597.94

5.38

0

0.365

0.711698

0.3072

0.867127

0.479535

0.503909

0.09729

0.945187

0.798859

2

1

2.4

75275.63

5.65

5

0.159

0.255814

0.011474

0.475471

0.005441

0.307059

0.023222

0.357511

0.003876

1

1

5.6

36775.57

5.76

0

0.384

0.387602

0.036408

1.07154

0.747081

0.169865

0.007017

0.979417

0.919196

3

2

9.9

31007.08

6.18

0

0.249

0.313034

0.019346

0.857395

0.448122

0.271538

0.017307

1.00367

0.995354

1

1

1.4

47712.98

7.96

0

0.783

0.230451

0.009008

0.788523

0.261431

0.213777

0.01048

0.870947

0.556883

1

1

0.8

5.95

0

0.5

0.309157

0.018692

0.313375

0.000275

0.209405

0.010077

0.739074

0.238649

1

1

1.7

57467.76

8.95

0

0.627

0.496984

0.083487

0.605733

0.036587

0.92838

0.734395

1.92957

0.000813

1

1

2.5

51677.47

5.82

0

0.611

0.469163

0.06834

0.419957

0.002116

0.11035

0.003965

0.323227

0.002353

161919.3

NSC 16186

SAC1_RAT

2

22 April 2015

DCAKD_RAT

Transmembrane emp24 domain-containing protein 10 OS = Rattus norvegicus GN = Tmed10 PE = 1 SV = 2 Dephospho-CoA kinase domain-containing protein OS = Rattus norvegicus GN = Dcakd PE = 2 SV = 1 Phosphatidylinositide phosphatase SAC1 OS = Rattus norvegicus GN = Sacm1l PE = 1 SV = 1 Proteasome (Prosome, macropain) 26S subunit, nonATPase, 6 OS = Rattus norvegicus GN = Psmd6 PE = 2 SV = 1 Cleft lip and palate associated transmembrane protein 1 OS = Rattus norvegicus GN = Clptm1 PE = 2 SV = 1 Fam49b protein OS = Rattus norvegicus GN = Fam49b PE = 2 SV = 1 Peroxiredoxin-4 OS = Rattus norvegicus GN = Prdx4 PE = 2 SV = 1 Uncharacterized protein OS = Rattus norvegicus PE = 2 SV = 1 Ubiquitin carboxyl-terminal hydrolase OS = Rattus norvegicus GN = Usp32 PE = 3 SV = 1 Brain-specific angiogenesis inhibitor 1-associated protein 2like protein 1 OS = Rattus norvegicus GN = Baiap2l1 PE = 2 SV = 1 Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform OS = Rattus norvegicus GN = Ppp2r2a PE = 2 SV = 1

X. Han et al. / Neuroscience xxx (2015) xxx–xxx No. of Pages 73

65

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

TMEDA_RAT

Protein kinase C and casein kinase

PACN1_RAT

Isoform 5 of Leucine-rich repeat-

LRRC7_RAT

LOC685144 protein

Protein Rab5c

Aa2-258

Glutamate receptor ionotropic,

B5DEG8_RAT

B0BNK1_RAT

Q7TP78_RAT

NMDE1_RAT

Serine/threonine-protein

PP1A_RAT

subunit

Threonine–tRNA ligase,

Vesicle-associated membrane

Q76LU9_RAT

VAMP2_RAT

Protein Tppp

Ndufa7 protein

Reticulon-3

A9UMV9_RAT

RTN3_RAT

protein kinase type II subunit beta

Calcium/calmodulin-dependent

D3ZQL7_RAT

KCC2B_RAT

Peptidyl-prolyl cis-trans isomerase

FKB1A_RAT

FKBP1A

Isoform 5 of Dynamin-1-like protein

DNM1L_RAT

(Predicted)

differentiation-associated-protein 1

Neurogranin

Ganglioside-induced

D4A5X7_RAT

M6-b

Neuronal membrane glycoprotein

NEUG_RAT

GPM6B_RAT

oxoglutarate/malate carrier protein

Mitochondrial 2-

alpha

Sn1-specific diacylglycerol lipase

M2OM_RAT

Synaptopodin

B1VKB4_RAT

DGLA_RAT

1

Disks large-associated protein 2

S-phase kinase-associated protein

DLGP2_RAT

SKP1_RAT

protein 2

Annexin A6

Glutathione peroxidase

ANXA6_RAT

mitochondrial

ERC protein 2

SYTM_RAT

subunit gamma

Guanine nucleotide-binding protein

7A2, mitochondrial

Cytochrome c oxidase subunit

D3ZMM4_RAT

G3V8K2_RAT

CX7A2_RAT

Vimentin

G3V8C3_RAT

phosphatase PP1-alpha catalytic

Cadherin-2

CADH2_RAT

NMDA 2A

Protein Sptbn4

F1LSL8_RAT

containing protein 7

Protein Syt7

Q99P36_RAT

Rtn3

Ndufa7

Tppp

Camk2b

Fkbp1a

6

8

3

15

2

4

5

Dnm1l

3

Gdap1

3

2

2

3

2

2

3

2

2

2

4

2

2

4

2

3

2

4

3

2

3

6

2

7

2

2

2

2

3

2

2

Nrgn

Gpm6b

Slc25a11

Dagla

Synpo

Skp1

Dlgap2

Vamp2

Gpx4

Anxa6

Tars2

Erc2

Gng3

Cox7a2

Ppp1ca

Vim

Cdh2

Grin2a

Ndufa8

Rab5c

Sec24c

Sptbn4

Lrrc7

Syt7

Pacsin1

Map6d1

Sec11a

Cnksr2

Unc13a

Atp5d

Tmed10

Dnaja2

2

peptides

Unique

10.6

52.7

15.6

31.9

15.7

7.1

14.0

26.9

8.5

8.0

3.5

7.6

11.0

2.8

35.3

13.0

2.2

3.2

6.5

32.0

18.1

13.3

3.4

5.6

2.0

20.1

15.1

3.3

1.4

6.4

6.9

21.5

15.7

10.6

2.8

1.8

16.7

7.8

5.6

27.6

coverage

Sequence

%

101515.7

12500.31

23546.3

60401.11

11922.49

82538.89

41216.11

7496.25

36196.32

34132.51

115300.1

96717.32

18671.82

118977.2

12690.64

29111.31

75753.3

81542.13

98023.61

8304.69

9352.87

37511.67

53700.03

99685.04

165466.7

21966.06

25178.31

118522.8

288312

158648.5

58160.81

50448.57

20412.55

20598.99

109695.9

194360.9

17562.79

24857.45

45765.11

8454.83

MW (Da)

5

10.48

9.45

6.73

7.89

6.51

8.86

6.53

5.76

9.89

6

9.69

4.4

6.3

7.84

10.31

5.39

8.24

6.41

7.65

10.28

5.94

5.06

4.61

6.59

8.39

8.24

6.71

5.73

6.01

9.35

5.15

9.94

9.15

6.09

5.15

5.16

6.01

6.06

10.07

pI

3

0

0

0

0

0

2

0

4

0

5

0

0

0

1

0

0

0

0

0

0

0

0

1

4

0

0

0

0

0

0

0

0

2

0

0

0

2

0

1

TMDs

1.75205 1.66864 1.56595

0.748 0.662 0.409

1.73409

1.41737 0.353

1.69747

0.266

1.28879

0.38

1.58853

0.394

1.37206

0.612

0.548

1.42587

3.60509

0.101

3.47943

0.077

2.32185

0.716 0.711

2.28604

0.868

2.18637

2.07201

0.004

0.236683

0.875

0.266841

0.432

1.97706

0.318

1.96822

0.308413

0.949

0.121

0.258

0.329001

0.301

0.345537

0.403

0.33738

0.348857

0.581

0.839

0.352696

0.309

1.90336

1.88383

0.347

0.35701

0.228

1.8738

0.593

1.86126

0.647

1.8529

1.02 0.532

1.84475

1.8394

1.82396

1.81562

1.81525

0.412416

0.416241

1.7896

Ratio

0.163808

0.098011

0.061826

0.068502

0.311065

0.083952

0.493531

0.147048

0.369551

0.300805

4.14E11

3.43E10

0.000892

0.001234

0.002916

0.007263

0.009565

0.012721

0.014603

0.015541

0.018569

0.022253

0.023925

0.024202

0.025656

0.026392

0.027264

0.027522

0.028275

0.029374

0.031841

0.033581

0.035356

0.036565

0.040251

0.042369

0.042467

0.044397

0.045752

0.049595

p-Value

Susceptible 113/115

0.516

0.119

0.728

0.554

0.211

0.127

0.695

0.108

GRAVY

1.89721

1.84332

1.84113

1.83977

1.82527

1.79993

1.76401

1.76185

1.75041

1.74927

1.26976

3.96524

1.99347

1.33779

1.47564

1.97087

0.312902

0.324403

1.26531

1.50322

0.205817

0.543782

0.32481

1.60723

0.523543

0.358642

0.770283

1.74991

0.550461

1.37116

1.46107

1.24948

1.67856

1.33804

1.49871

2.07493

2.16807

0.685581

0.570725

1.94724

Ratio

0.017599

0.026072

0.02648

0.026737

0.029609

0.035264

0.044843

0.045485

0.049004

0.049367

0.521404

6.21E16

0.008296

0.407061

0.226375

0.009955

0.024348

0.026701

0.52941

0.198474

0.009757

0.124969

0.026787

0.115683

0.110236

0.034903

0.406256

0.049162

0.130153

0.356938

0.242198

0.558424

0.076706

0.40668

0.202854

0.004173

0.001796

0.274098

0.14691

0.012

p-Value

Susceptible 116/118

1.34355

2.04391

1.69424

0.63483

0.5967

0.59831

0.55128

0.83019

Ratio

115

0.118429

2.02E06

0.001585

0.052821

0.032505

0.033202

0.017384

0.366774

p-value

Unsusceptible 114/

1.56141

1.49719

1.74609

0.550054

0.67227

0.764273

0.628846

0.511518

Ratio

0.043456

0.073864

0.007231

0.042834

0.139486

0.286668

0.094469

0.027949

p-Value

Unsusceptible 117/118

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

localization

Membrane

p

p

p

p

p

p

p

p

p

p

active zone

proteins

p

Presynaptic

Presynaptic

Synaptic localization

p

p

vesicles

Synaptic

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

density

Postsynaptic

66

substrate in neurons protein 1

Protein Map6d1

subunit SEC11A

Signal peptidase complex catalytic

suppressor of ras 2

Connector enhancer of kinase

homolog A

Isoform 3 of Protein unc-13

mitochondrial

ATP synthase subunit delta,

containing protein 10

Transmembrane emp24 domain-

member 2

DnaJ homolog subfamily A

2

D3ZT16_RAT

SC11A_RAT

CNKR2_RAT

UN13A_RAT

G3V7Y3_RAT

TMEDA_RAT

DNJA2_RAT

Cox6c2

Cytochrome c oxidase subunit 6C-

CX6C2_RAT

Gene

name

Protein name

number

Accession

Appendix Table 3a. Differentially expressed membrane proteins (74 proteins) identified from the susceptible and unsusceptible groups through iTRAQ-based quantitative proteomics. MW, molecular weight; pI, isoelectric point; TMDs, transmembrane domains; GRAVY, grand average hydropathicity

NSC 16186 No. of Pages 73

22 April 2015

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

isoform CRA_b

protein homolog 1 (C. elegans),

Succinate dehydrogenase

Gamma-aminobutyric acid

Aggrecan core protein

Protein Slc1a4 (Fragment)

NADH-ubiquinone oxidoreductase

D4A7Y1_RAT

Q76GL9_RAT

Q06QG6_RAT

Claudin 11 (Fragment)

Glutamate receptor, metabotropic

Q924Y3_RAT

B2CZC8_RAT

Aspartate aminotransferase,

AATM_RAT

D3ZD09_RAT

Protein Slc25a22

D3ZRF5_RAT

Cytochrome c oxidase subunit 6B1

mitochondrial

Isoform 1 of Gamma-adducin

Alpha-1-antiproteinase

A1AT_RAT

dehydrogenase, mitochondrial

Long-chain specific acyl-CoA

(Fragment)

Contactin-associated protein 1

1

Neutral cholesterol ester hydrolase

brain isoform

V-type proton ATPase subunit B,

mitochondrial

ATP synthase subunit d,

(Fragment)

Palmitoyl-protein thioesterase 1

ADDG_RAT

ACADL_RAT

CNTP1_RAT

NCEH1_RAT

VATB2_RAT

ATP5H_RAT

PPT1_RAT

Ras-related protein Rab-12

D4A376_RAT

5, isoform CRA_a

Peroxiredoxin-1

PRDX1_RAT

chain 5

Adenylate kinase isoenzyme 1

KAD1_RAT

gamma (Fragment)

protein kinase type II subunit

Calcium/calmodulin-dependent

receptor subunit beta-2

GBRB2_RAT

F1LUE2_RAT

CD9 antigen

Protein Opalin

CD9_RAT

GABA transporter 1

Sodium- and chloride-dependent

mitochondrial

pyruvate dehydrogenase complex,

acetyltransferase component of

Dihydrolipoyllysine-residue

Q56A26_RAT

SC6A1_RAT

ODP2_RAT

Peptidyl-prolyl cis-trans isomerase

PPIB_RAT

B

Cytochrome P450 4F4

CP4F4_RAT

mitochondrial

[ubiquinone] iron-sulfur subunit,

Band 3 anion exchange protein

DHSB_RAT

exchanger 2

Sodium/potassium/calcium

Q91ZE7_RAT

NCKX2_RAT

4-nitrophenylphosphatase domain

G3V728_RAT

and non-neuronal SNAP25-like

V-type proton ATPase subunit E 1

Protein Copa

G3V6T1_RAT

reductase 3

Isoform 2 of NADH-cytochrome b5

VATE1_RAT

NB5R3_RAT

Cox6b1

Got2

Slc25a22

Serpina1

Add3

Acadl

Cntnap1

Nceh1

Atp6v1b2

Atp5h

Ppt1

Grm5

Cldn11

Rab12

Prdx1

Mt-nd5

Slc1a4

Acan

Ak1

Camk2g

Gabrb2

Opalin

Cd9

Slc6a1

Dlat

Ppib

Cyp4f4

Sdhb

Slc4a1

3

17

10

2

2

3

2

3

13

8

2

2

2

2

8

3

3

2

5

8

3

2

2

2

12

4

2

5

3

2

5

Nipsnap1

Slc24a2

2

7

2

Copa

Atp6v1e1

Cyb5r3

37.2

38.8

34.1

4.1

4.8

7.4

3.1

9.3

29.9

44.7

11.8

1.6

14.4

21.4

34.7

7.9

6.6

1.0

32.0

16.7

7.8

21.8

10.2

8.4

18.8

19.0

4.0

18.1

4.8

3.4

17.6

2.4

22.6

9.5

10071.35

47313.74

34661.99

46135.27

75360.54

47872.31

149647.2

45821.25

56550.16

18763.21

31531.1

131884

12040.45

16143.51

22109.14

68587.28

56137.88

223896

21583.52

53592.45

54632.84

15672.53

25214.65

67000.71

67165.04

23802.3

60822.84

31829.64

94311.68

74655.81

33345.9

138358.3

26128.12

34865.15

8.96

9.13

9.26

5.7

5.75

7.63

6.44

6.56

5.57

6.16

6.72

8.07

8.62

9.86

8.27

9.34

6.38

4.16

7.66

7.39

9.35

4.98

6.93

8.25

8.76

9.5

7.24

8.96

5.83

5.93

9.44

7.69

8.44

8.56

0

0

2

0

0

0

0

1

0

0

0

6

1

0

0

15

10

0

0

0

4

1

4

12

0

1

2

0

10

11

0

0

0

0

1.63347

0.596

0.327

0.338857

0.764

0.23

0.179

1.39114

1.22532

1.29793

0.70252 1.35396

0.543

1.20786

0.69692

1.28784

1.31607

1.90881

0.158

0.223

0.306

0.007

0.176

0.702

1.90674

1.90447

0.146

0.33107

0.777

0.48849

0.477 0.107

1.57432

1.54435

0.222

0.621

0.55061

0.55374

0.377 0.529

1.51853

0.43

1.51285

0.56393

0.42

0.068

0.61128

1.43714

1.88387

1.66788

2.31773

1.61803

1.49147

0.037602

1.05E19

3.03E06

0.000189

0.003193

0.004089

0.004493

0.012247

0.013993

0.58465

0.368401

4.32687

2.72809

2.38937

2.10525

2.07727

2.06645

1.94464

1.92744

0.537

0.024231

0.475429

0.319598

0.28521

0.1216

0.117636

0.092359

0.165295

0.565506

0.376

0.468

0.017

1.30014

0.202

1.41043

1.43918

0.147

0.37

1.62693

1.6798

0.209

1.56403

0.279

1.24571

0.49

0.213

0.075377

0.306347

0.175852

0.107653

0.114534

0.345494

0.107888

0.190993

0.150929

3.53E05

3.68E05

3.85E05

0.000394

0.006712

0.008989

0.013287

0.017218

0.018006

0.018355

0.019673

0.020803

0.025409

0.027671

0.039304

0.046849

5.76E05

0.002377

1.99E09

0.00493

1.87299

1.76443

1.71517

1.68155

0.51055

1.60344

0.519136

1.55566

1.54945

1.92459

1.54995

1.38223

0.377782

0.469181

1.2538

1.39349

0.618312

0.553109

2.14985

1.7957

0.483

1.5213

0.663898

0.688171

1.46697

1.47305

3.20927

3.28321

1.96348

0.001666

0.00592

0.010043

0.014167

0.027642

0.029929

0.030475

0.045661

0.048142

0.000867

0.047937

0.169928

0.005154

0.016954

0.363457

0.157635

0.085527

0.044258

3.42E05

0.004169

0.02003

0.060862

0.129717

0.159588

0.093277

0.089076

1.61E15

1.79E16

0.000519

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

Membrane

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

p

NSC 16186 No. of Pages 73

22 April 2015

X. Han et al. / Neuroscience xxx (2015) xxx–xxx 67

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

Peptidyl-prolyl cis-trans isomerase D Dead end homolog 1 (Zebrafish) 60S acidic ribosomal protein P2 Ubiquitin thioesterase OTUB1 DEAD (AspGlu-Ala-Asp) box polypeptide 3 Y-linked Saccharopine dehydrogenaselike oxidoreductase Guanine nucleotidebinding protein G(I)/G(S)/G(T) subunit beta-3 Peroxiredoxin-4 Non-specific lipid-transfer protein Stathmin Actin-related protein 2 Protein Sh3bgrl3 Rps16 protein (Fragment) Parathymosin Protein NDRG2 Ubiquitin carboxylterminal hydrolase CYLD Mthfd1l protein Actin-related protein 2/3 complex subunit 5 Alpha-1inhibitor 3 NADH dehydrogenase (Ubiquinone) 1 beta subcomplex, 11 (Predicted) Malic enzyme

Q4QQV4_RAT

RLA2_RAT

OTUB1_RAT

C9WPN2_RAT

SCPDL_RAT

GBB3_RAT

PRDX4_RAT NLTP_RAT

STMN1_RAT ARP2_RAT B2RZ27_RAT Q5XFV9_RAT PTMS_RAT NDRG2_RAT CYLD_RAT

B2GUZ3_RAT ARPC5_RAT

A1I3_RAT D4A7L4_RAT

D3ZJH9_RAT

Unique peptides

% Sequence coverage

Ppid

2

4.9

40765.22

6.73

0

Hars

2

4.9

57359.55

5.86

Rplp2

2

20.9

11691.82

Otub1

3

7.8

Ddx3y

3

Sccpdh

MW (Da)

pI

TMDs

GRAVY

Susceptible 113/115

Susceptible 116/118

Unsusceptible 114/115

Ratio

p-Value

0.421

0.41661

0.045884

0.636291

0.212464

Nonmembrane

0

0.309

0.416308

0.0457753

0.402199

0.0483645

Nonmembrane

4.44

0

0.263

0.411142

0.0439535

0.356717

0.0343902

Nonmembrane

31269.66

4.85

0

0.553

0.405167

0.0419231

0.388892

0.0438526

Nonmembrane

6.8

73005.64

6.67

0

0.666

0.396328

0.0390653

0.608784

0.182766

Nonmembrane

2

9.9

35411.12

8.09

0

0.12

1.85696

0.0327266

1.55531

0.152779

Nonmembrane

Gnb3

3

8.5

37179.75

5.51

0

0.077

0.342908

0.0250867

0.538834

0.121232

Prdx4 Scp2

2 2

9.9 2.6

31007.08 58812.68

6.18 6.62

0 0

0.249 0.222

0.313034 0.272637

0.0193455 0.0134236

0.271538 0.296006

0.0173069 0.0212171

Nonmembrane Nonmembrane

Stmn1 Actr2

2 3

16.1 15.7

17288.28 32490.99

5.76 6.15

0 0

1.313 0.123

2.00308 2.04618

0.0121239 0.00882984

1.91688 1.79542

0.0151699 0.036362

Nonmembrane Nonmembrane

Sh3bgrl3

2

29.0

10476.63

5.02

0

0.522

2.12015

0.00499369

2.37561

0.00021979

Nonmembrane

Rps16

2

13.2

17899.83

10.21

0

0.342

3.11855

8.48E08

2.41858

0.00013685

Nonmembrane

Ptms Ndrg2 Cyld

2 3 2

22.6 13.2 2.9

11558.77 40778.74 106711.4

4.15 5.16 5.44

0 0 0

2.047 0.272 0.354

1.4956 1.34479 1.7638

0.22523 0.407849 0.0577538

1.85037 1.85857 2.0484

0.0247932 0.023374 0.00524639

Nonmembrane Nonmembrane Nonmembrane

Mthfd1l Arpc5

2 2

2.6 21.2

105840.9 16320.23

7.29 5.47

0 0

0.092 0.404

1.67336

0.0955869

2.27685

0.00062077

A1i3

2

2.2

163771.4

5.7

0

Ndufb11

2

25.8

17633.8

5.17

Me2

2

4.3

65350.91

7.87

0.587079

0.028593

Ratio

0.785498

p-Value

Membrane localization

p-Value

Ratio

p-Value

Unsusceptible 117/118

Ratio

0.331869

Nonmembrane

1.43661

0.0471138

1.43573

0.117448

Nonmembrane Nonmembrane

0.216

1.44416

0.0434176

1.56611

0.0417258

Nonmembrane

0

0.436

0.593568

0.0311841

0.729673

0.222277

Nonmembrane

0

0.148

1.47671

0.0301663

1.20207

0.470262

Nonmembrane

No. of Pages 73

PPID_RAT

Gene name

NSC 16186

Protein name

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Accession number

22 April 2015

68

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

Appendix Table 3b. Differentially expressed nonmembrane proteins (35 proteins) identified from the susceptible and unsusceptible groups through iTRAQ-based quantitative proteomics

HBB1_RAT HBB2_RAT Q62669_RAT Q5XI17_RAT B4F7C2_RAT TBB3_RAT 1433T_RAT Q4QQV0_RAT STIP1_RAT

F1LM47_RAT PPIA_RAT

9

24.6

33138.25

9.49

0

Acot7

5

13.2

39055.46

8.38

0

Hba1

10

60.6

15328.35

7.81

Hbb

10

75.5

15979.19

N/A

10

74.2

Hbb-b1 Tarsl2 Tubb4 Tubb3

5 2 19 18

Ywhaq

0.056

1.54146

0.0137857

1.50442

0.0697445

Nonmembrane

0.36

1.63505

0.00386339

1.31529

0.258151

Nonmembrane

0

0.115

1.68349

0.00187259

2.13924

4.04E05

Nonmembrane

7.87

0

0.042

1.72359

0.0009935

2.24838

6.82E06

Nonmembrane

15982.24

8.91

0

0.003

1.9311

2.26E05

2.69229

1.05E09

Nonmembrane

32.0 2.5 48.7 39.1

16022.32 64118.31 49585.25 50418.13

7.93 7.89 4.78 4.82

0 0 0 0

0.001 0.657 0.321 0.371

2.13809 2.3531 1.30015 1.25815

2.22E07 7.30E10 0.172646 0.241011

3.08147 1.94015 1.54997 1.59416

6.06E14 0.000707803 0.0479303 0.0325559

Nonmembrane Nonmembrane Nonmembrane Nonmembrane

7

24.9

27777.97

4.69

0

0.512

1.2445

0.266892

1.66904

0.016048

Nonmembrane

Tubb6 Stip1

11 3

25.1 5.2

50058.83 62569.41

4.8 6.4

0 0

0.344 0.945

1.32657 1.2081

0.137786 0.344935

1.69051 1.74467

0.0129423 0.00734337

Nonmembrane Nonmembrane

Sucla2

12

23.3

47286.13

6.08

0

0.026

1.35867

0.103039

1.80977

0.00354687

Nonmembrane

Ppia

12

65.9

17874.13

8.34

0

0.326

1.2499

0.256441

1.82094

0.00311451

Nonmembrane

Appendix Table 3b. Differentially expressed proteins without known localization (4 proteins) from the susceptible and unsusceptible groups through iTRAQ-based quantitative proteomics Accession number

Protein name

CNRP1_RAT

CB1 cannabinoid receptorinteracting protein 1 Protein Efr3b (Fragment) Protein Rftn2 Protein IMPACT

F1M5F9_RAT D3ZII1_RAT IMPCT_RAT

Gene name

Unique peptides

% Sequence coverage

MW (Da)

pI

TMDs

Cnrip1

2

15.9

18987.71

9.45

0

Efr3b Rftn2 Impact

2 2 2

3.8 8.5 7.6

87513.01 54746.58 35994.52

6.39 5.25 5.07

0 0 0

GRAVY

Susceptible 113/115

Susceptible 116/118

NSC 16186

HBA_RAT

Auh

22 April 2015

BACH_RAT

Protein Auh (Fragment) Cytosolic acyl coenzyme A thioester hydrolase Hemoglobin subunit alpha-1/ 2 Hemoglobin subunit beta-1 Hemoglobin subunit beta-2 Protein Hbb-b1 Protein Tarsl2 RCG45085 Tubulin beta-3 chain 14-3-3 protein theta Protein Tubb6 Stress-inducedphosphoprotein 1 Protein Sucla2 (Fragment) Peptidyl-prolyl cis-trans isomerase A

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Membrane localization

Ratio

p-Value

Ratio

p-Value

0.341

0.373902

0.0325476

0.386928

0.0432178

Unknown

0.175 0.552 0.593

1.95817 2.32033 2.35611

0.0166728 0.00090478 0.000649819

1.28001 1.59251 1.82125

0.503185 0.125398 0.0304501

Unknown Unknown Unknown

No. of Pages 73

69

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

F1LU71_RAT

NSC 16186

No. of Pages 73

22 April 2015

70

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

Appendix Table 4. Summative description of the research literature and studies regarding the associations between the differentially expressed PSDrelated proteins and mental disorders Gene name

Related to depression

Dnaja2 Atp5d Unc13a Cnksr2 Pacsin1 Sptbn4 Sec24c Grin2a

Prefrontal cortex of patients with major depression and bipolar disorder (Lee et al., 2011) Brain tissue of post-stroke depression rat model (Zhao et al., 2013), frontal cortex and hippocampus of unpredictable chronic mild stress rat model (Lou et al., 2010)

Cdh2 Ppp1ca Gng3 Gpx4 Vamp2

Dlgap2 Synpo

Frontal cortex of major depressive patients treated with fluvoxamine (Saito et al., 2006), frontal cortex and hippocampus of electroconvulsive therapy rat model (Elfving et al., 2008) Prefrontal cortex of patients with major depression and bipolar disorder (Lee et al., 2011) Postmortem hippocampus CA3 of depression patients (Soetanto et al., 2010)

Slc25a11 Nrgn Dnm1l Lrrc7 Camk2b

Tppp Rtn3 Atp6v1e1

Slc4a1 Camk2g Ak1

Postmortem frontal cerebral cortex tissues from severe depression patients (Novak et al., 2006), lateral habenula of animal models of depression (Li et al., 2013) Saliva of maltreated children with depression (Weder et al., 2014)

Schizophrenia (Rippey et al., 2013; Martin et al., 2014) Schizophrenia (Martin et al., 2014), Alzheimer’s disease (Ding et al., 2014; Suszynska-Zajczyk et al., 2014) Schizophrenia (Focking et al., 2014), amyotrophic lateral sclerosis (Diekstra et al., 2012; Su et al., 2014) Intellectual, attention, and language deficits (Vaags et al., 2014) Huntington’s disease (Caron et al., 2013; Marco et al., 2013) Alzheimer’s disease (Sanchez-Mut et al., 2013) Alzheimer’s disease (Morgan et al., 2007) Schizophrenia (Tang et al., 2006; Wright et al., 2013; Barkus et al., 2014), Huntington’s disease (Saft et al., 2011), bipolar disorder (Itokawa et al., 2003), anxiety (Park et al., 2013) Anxiety (Danglot et al., 2012), Alzheimer’s disease (Ando et al., 2011), Huntington’s disease (Reis et al., 2011) Alzheimer’s disease (Kakiya et al., 2012; BanzhafStrathmann et al., 2014) Seizures (Schwindinger et al., 2004) Huntington’s disease (Cong et al., 2012), Alzheimer’s disease (Yoo et al., 2010) Alzheimer’s disease (Chen et al., 2008; Shi et al., 2012; Koldamova et al., 2014), anxiety (Valdez et al., 2007)

Schizophrenia (Li et al., 2014), autism (Chien et al., 2013; Jiang-Xie et al., 2014) Schizophrenia (Focking et al., 2014), anxiety (Soetanto et al., 2010) Schizophrenia (Focking et al., 2014) Schizophrenia (Thong et al., 2013; Walton et al., 2013), anxiety (Miyakawa et al., 2001; Wilcoxon et al., 2007) Alzheimer’s disease (Gan et al., 2014), Huntington’s disease (Guo et al., 2013) Schizophrenia (Carlisle et al., 2011), autism (Carlisle et al., 2011) Schizophrenia (Novak et al., 2006; Focking et al., 2014), anxiety (Choi et al., 2011) Alzheimer’s disease (Olah et al., 2011), autism (Iurov et al., 2010) Alzheimer’s disease (Masliah et al., 2010; Araki et al., 2013)

Hippocampus of social defeat rat model (Carboni et al., 2006), anterior cingulate cortex of patients with major depression (Beasley et al., 2006), synaptosomes of prefrontal/frontal cortex and hippocampus of learned helplessness rat model (Mallei et al., 2011) Hippocampus of mice treated with paroxetine (Sillaber et al., 2008) Synaptosomes of prefrontal/frontal cortex and hippocampus of learned helplessness rat model (Mallei et al., 2011)

Prdx1

Grm5

Related to other mental disorders

Locus coeruleus of postmortem patients with major depressive disorder (Chandley et al., 2014), brain molecular imaging of sleep-deprived human with depression (Hefti et al., 2013), antidepressant administrated mice (PomiernyChamiolo et al., 2010), hippocampus of rat injected with corticosterone (Iyo et al., 2010)

Schizophrenia (Focking et al., 2014) Alzheimer’s disease (Park et al., 2012), Huntington’s disease (Brackenridge et al., 1978) Alzheimer’s disease (Cumming et al., 2007), Huntington’s disease (Pitts et al., 2012), schizophrenia (Focking et al., 2014) Alzheimer’s disease (Hamilton et al., 2014), schizophrenia (Turlington et al., 2014; Yu et al., 2014), Huntington’s disease (Doria et al., 2013), anxiety (Felts et al., 2013; Kumar et al., 2013)

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

NSC 16186

No. of Pages 73

22 April 2015

X. Han et al. / Neuroscience xxx (2015) xxx–xxx Atp5h Atp6v1b2

Blood of major depressive disorder patients (Shyn et al., 2011)

Cntnap1 Slc25a22 Got2 Vim

Monocyte of depressed patients (Cervera Enguix et al., 1995), hippocampus of mice treated with paroxetine (Sillaber et al., 2008), embryonic stem cell-derived neural cells exposed to antidepressant paroxetine (McHugh et al., 2008)

71

Alzheimer’s disease (Boada et al., 2014) Schizophrenia (Ji et al., 2009), Alzheimer’s disease (Coffey et al., 2014) Alzheimer’s disease (Fan et al., 2013) Seizures (Mastrangelo and Leuzzi, 2012; Poduri et al., 2013) Schizophrenia (Tsai et al., 2007; Wesseling et al., 2013), anxiety (Owada et al., 2006) Alzheimer’s disease (Kamphuis et al., 2012; Shan et al., 2012), anxiety (Lalonde and Strazielle, 2003)

REFERENCES Ando K, Uemura K, Kuzuya A, Maesako M, Asada-Utsugi M, Kubota M, Aoyagi N, Yoshioka K, Okawa K, Inoue H, Kawamata J, Shimohama S, Arai T, Takahashi R, Kinoshita A (2011) N-cadherin regulates p38 MAPK signaling via association with JNK-associated leucine zipper protein: implications for neurodegeneration in Alzheimer disease. J Biol Chem 286:7619–7628. Araki W, Oda A, Motoki K, Hattori K, Itoh M, Yuasa S, Konishi Y, Shin RW, Tamaoka A, Ogino K (2013) Reduction of beta-amyloid accumulation by reticulon 3 in transgenic mice. Curr Alzheimer Res 10:135–142. Banzhaf-Strathmann J, Benito E, May S, Arzberger T, Tahirovic S, Kretzschmar H, Fischer A, Edbauer D (2014) MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer’s disease. EMBO J 33:1667–1680. Barkus C, Sanderson DJ, Rawlins JN, Walton ME, Harrison PJ, Bannerman DM (2014) What causes aberrant salience in schizophrenia? A role for impaired short-term habituation and the GRIA1 (GluA1) AMPA receptor subunit. Mol Psychiatry 19:1060–1070. Beasley CL, Pennington K, Behan A, Wait R, Dunn MJ, Cotter D (2006) Proteomic analysis of the anterior cingulate cortex in the major psychiatric disorders: Evidence for disease-associated changes. Proteomics 6:3414–3425. Boada M, Antunez C, Ramirez-Lorca R, DeStefano AL, Gonzalez-Perez A, Gayan J, Lopez-Arrieta J, Ikram MA, Hernandez I, Marin J, Galan JJ, Bis JC, Mauleon A, Rosende-Roca M, Moreno-Rey C, Gudnasson V, Moron FJ, Velasco J, Carrasco JM, Alegret M, Espinosa A, Vinyes G, Lafuente A, Vargas L, Fitzpatrick AL, Launer LJ, Saez ME, Vazquez E, Becker JT, Lopez OL, Serrano-Rios M, Tarraga L, van Duijn CM, Real LM, Seshadri S, Ruiz A (2014) ATP5H/KCTD2 locus is associated with Alzheimer’s disease risk. Mol Psychiatry 19:682–687. Brackenridge CJ, Case J, Chiu E, Propert DN, Teltscher B, Wallace DC (1978) A linkage study of the loci for Huntington’s disease and some common polymorphic markers. Ann Hum Genet 42:203–211. Carboni L, Piubelli C, Pozzato C, Astner H, Arban R, Righetti PG, Hamdan M, Domenici E (2006) Proteomic analysis of rat hippocampus after repeated psychosocial stress. Neuroscience 137:1237–1246. Carlisle HJ, Luong TN, Medina-Marino A, Schenker L, Khorosheva E, Indersmitten T, Gunapala KM, Steele AD, O’Dell TJ, Patterson PH, Kennedy MB (2011) Deletion of densin-180 results in abnormal behaviors associated with mental illness and reduces mGluR5 and DISC1 in the postsynaptic density fraction. J Neurosci 31:16194–16207. Caron NS, Desmond CR, Xia J, Truant R (2013) Polyglutamine domain flexibility mediates the proximity between flanking sequences in huntingtin. Proc Natl Acad Sci U S A 110:14610–14615. Cervera Enguix S, Rodriguez-Rosado A, Ramos Ruiz F, Sarrais Oteo F, Pla Vidal J, Rodriguez-Rosado R (1995) [Study of the evolution of some monocytic parameters and neuroendocrine function tests in depressed patients]. Actas Luso Esp Neurol Psiquiatr Cienc Afines 23:67–73. Chandley MJ, Szebeni A, Szebeni K, Crawford JD, Stockmeier CA, Turecki G, Kostrzewa RM, Ordway GA (2014) Elevated gene expression of glutamate receptors in noradrenergic neurons from the locus coeruleus in major depression. Int J Neuropsychopharmacol 17:1569–1578. Chen L, Na R, Gu M, Richardson A, Ran Q (2008) Lipid peroxidation up-regulates BACE1 expression in vivo: a possible early event of amyloidogenesis in Alzheimer’s disease. J Neurochem 107:197–207. Chien WH, Gau SS, Liao HM, Chiu YN, Wu YY, Huang YS, Tsai WC, Tsai HM, Chen CH (2013) Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders. Mol Autism 4:26. Choi K, Le T, Xing G, Johnson LR, Ursano RJ (2011) Analysis of kinase gene expression in the frontal cortex of suicide victims: implications of fear and stress. Front Behav Neurosci 5:46. Coffey EE, Beckel JM, Laties AM, Mitchell CH (2014) Lysosomal alkalization and dysfunction in human fibroblasts with the Alzheimer’s disease-linked presenilin 1 A246E mutation can be reversed with cAMP. Neuroscience 263:111–124. Cong WN, Cai H, Wang R, Daimon CM, Maudsley S, Raber K, Canneva F, von Horsten S, Martin B (2012) Altered hypothalamic protein expression in a rat model of Huntington’s disease. PLoS One 7:e47240. Cumming RC, Dargusch R, Fischer WH, Schubert D (2007) Increase in expression levels and resistance to sulfhydryl oxidation of peroxiredoxin isoforms in amyloid betaresistant nerve cells. J Biol Chem 282:30523–30534. Danglot L, Freret T, Le Roux N, Narboux Neme N, Burgo A, Hyenne V, Roumier A, Contremoulins V, Dauphin F, Bizot JC, Vodjdani G, Gaspar P, Boulouard M, Poncer JC, Galli T, Simmler MC (2012) Vezatin is essential for dendritic spine morphogenesis and functional synaptic maturation. J Neurosci 32:9007–9022. Diekstra FP, van Vught PW, van Rheenen W, Koppers M, Pasterkamp RJ, van Es MA, Schelhaas HJ, de Visser M, Robberecht W, Van Damme P, Andersen PM, van den Berg LH, Veldink JH (2012) UNC13A is a modifier of survival in amyotrophic lateral sclerosis. Neurobiol Aging 33:630 e633–638. Ding B, Xi Y, Gao M, Li Z, Xu C, Fan S, He W (2014) Gene expression profiles of entorhinal cortex in Alzheimer’s disease. Am J Alzheimers Dis Other Demen 29:526–532. Doria JG, Silva FR, de Souza JM, Vieira LB, Carvalho TG, Reis HJ, Pereira GS, Dobransky T, Ribeiro FM (2013) Metabotropic glutamate receptor 5 positive allosteric modulators are neuroprotective in a mouse model of Huntington’s disease. Br J Pharmacol 169:909–921. Elfving B, Bonefeld BE, Rosenberg R, Wegener G (2008) Differential expression of synaptic vesicle proteins after repeated electroconvulsive seizures in rat frontal cortex and hippocampus. Synapse 62:662–670. Fan LF, Xu DE, Wang WH, Yan K, Wu H, Yao XQ, Xu RX, Liu CF, Ma QH (2013) Caspr interaction with Amyloid Precursor Protein reduces amyloid-beta generation in vitro. Neurosci Lett 548:255–260. Felts AS, Rodriguez AL, Morrison RD, Venable DF, Manka JT, Bates BS, Blobaum AL, Byers FW, Daniels JS, Niswender CM, Jones CK, Conn PJ, Lindsley CW, Emmitte KA (2013) Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety. Bioorg Med Chem Lett 23:5779–5785. Focking M, Lopez LM, English JA, Dicker P, Wolff A, Brindley E, Wynne K, Cagney G, Cotter DR (2014) Proteomic and genomic evidence implicates the postsynaptic density in schizophrenia. Mol Psychiatry. Gan X, Huang S, Wu L, Wang Y, Hu G, Li G, Zhang H, Yu H, Swerdlow RH, Chen JX, Yan SS (2014) Inhibition of ERK-DLP1 signaling and mitochondrial division alleviates mitochondrial dysfunction in Alzheimer’s disease cybrid cell. Biochim Biophys Acta 1842:220–231. Guo X, Disatnik MH, Monbureau M, Shamloo M, Mochly-Rosen D, Qi X (2013) Inhibition of mitochondrial fragmentation diminishes Huntington’s disease-associated neurodegeneration. J Clin Invest 123:5371–5388. Hamilton A, Esseltine JL, DeVries RA, Cregan SP, Ferguson SS (2014) Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer’s disease. Mol Brain 7:40. Hefti K, Holst SC, Sovago J, Bachmann V, Buck A, Ametamey SM, Scheidegger M, Berthold T, Gomez-Mancilla B, Seifritz E, Landolt HP (2013) Increased metabotropic

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

NSC 16186

No. of Pages 73

22 April 2015

72

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

glutamate receptor subtype 5 availability in human brain after one night without sleep. Biol Psychiatry 73:161–168. Itokawa M, Yamada K, Iwayama-Shigeno Y, Ishitsuka Y, Detera-Wadleigh S, Yoshikawa T (2003) Genetic analysis of a functional GRIN2A promoter (GT)n repeat in bipolar disorder pedigrees in humans. Neurosci Lett 345:53–56. Iurov I, Vorsanova SG, Saprina EA, Iurov Iu B (2010) [Identification of candidate genes of autism on the basis of molecular cytogenetic and in silico studies of the genome organization of chromosomal regions involved in unbalanced rearrangements]. Genetika 46:1348–1351. Iyo AH, Feyissa AM, Chandran A, Austin MC, Regunathan S, Karolewicz B (2010) Chronic corticosterone administration down-regulates metabotropic glutamate receptor 5 protein expression in the rat hippocampus. Neuroscience 169:1567–1574. Ji B, La Y, Gao L, Zhu H, Tian N, Zhang M, Yang Y, Zhao X, Tang R, Ma G, Zhou J, Meng J, Ma J, Zhang Z, Li H, Feng G, Wang Y, He L, Wan C (2009) A comparative proteomics analysis of rat mitochondria from the cerebral cortex and hippocampus in response to antipsychotic medications. J Proteome Res 8:3633–3641. Jiang-Xie LF, Liao HM, Chen CH, Chen YT, Ho SY, Lu DH, Lee LJ, Liou HH, Fu WM, Gau SS (2014) Autism-associated gene Dlgap2 mutant mice demonstrate exacerbated aggressive behaviors and orbitofrontal cortex deficits. Mol Autism 5:32. Kakiya N, Saito T, Nilsson P, Matsuba Y, Tsubuki S, Takei N, Nawa H, Saido TC (2012) Cell surface expression of the major amyloid-beta peptide (Abeta)-degrading enzyme, neprilysin, depends on phosphorylation by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) and dephosphorylation by protein phosphatase 1a. J Biol Chem 287:29362–29372. Kamphuis W, Mamber C, Moeton M, Kooijman L, Sluijs JA, Jansen AH, Verveer M, de Groot LR, Smith VD, Rangarajan S, Rodriguez JJ, Orre M, Hol EM (2012) GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease. PLoS One 7:e42823. Koldamova R, Schug J, Lefterova M, Cronican AA, Fitz NF, Davenport FA, Carter A, Castranio EL, Lefterov I (2014) Genome-wide approaches reveal EGR1-controlled regulatory networks associated with neurodegeneration. Neurobiol Dis 63:107–114. Kumar J, Hapidin H, Bee YT, Ismail Z (2013) Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like syndrome in rats. Behav Brain Funct 9:43. Lalonde R, Strazielle C (2003) Neurobehavioral characteristics of mice with modified intermediate filament genes. Rev Neurosci 14:369–385. Lee SA, Tsao TT, Yang KC, Lin H, Kuo YL, Hsu CH, Lee WK, Huang KC, Kao CY (2011) Construction and analysis of the protein-protein interaction networks for schizophrenia, bipolar disorder, and major depression. BMC Bioinformatics 12 Suppl 13:S20. Li JM, Lu CL, Cheng MC, Luu SU, Hsu SH, Hu TM, Tsai HY, Chen CH (2014) Role of the DLGAP2 gene encoding the SAP90/PSD-95-associated protein 2 in schizophrenia. PLoS One 9:e85373. Li K, Zhou T, Liao L, Yang Z, Wong C, Henn F, Malinow R, Yates JR, 3rd, Hu H (2013) betaCaMKII in lateral habenula mediates core symptoms of depression. Science 341:1016–1020. Lou JS, Li CY, Yang XC, Fang J, Yang YX, Guo JY (2010) Protective effect of gan mai da zao decoction in unpredictable chronic mild stress-induced behavioral and biochemical alterations. Pharm Biol 48:1328–1336. Mallei A, Giambelli R, Gass P, Racagni G, Mathe AA, Vollmayr B, Popoli M (2011) Synaptoproteomics of learned helpless rats involve energy metabolism and cellular remodeling pathways in depressive-like behavior and antidepressant response. Neuropharmacology 60:1243–1253. Marco S, Giralt A, Petrovic MM, Pouladi MA, Martinez-Turrillas R, Martinez-Hernandez J, Kaltenbach LS, Torres-Peraza J, Graham RK, Watanabe M, Lujan R, Nakanishi N, Lipton SA, Lo DC, Hayden MR, Alberch J, Wesseling JF, Perez-Otano I (2013) Suppressing aberrant GluN3A expression rescues synaptic and behavioral impairments in Huntington’s disease models. Nat Med 19:1030–1038. Martin DA, Marona-Lewicka D, Nichols DE, Nichols CD (2014) Chronic LSD alters gene expression profiles in the mPFC relevant to schizophrenia. Neuropharmacology 83:1–8. Masliah E, Xie F, Dayan S, Rockenstein E, Mante M, Adame A, Patrick CM, Chan AF, Zheng B (2010) Genetic deletion of Nogo/Rtn4 ameliorates behavioral and neuropathological outcomes in amyloid precursor protein transgenic mice. Neuroscience 169:488–494. Mastrangelo M, Leuzzi V (2012) Genes of early-onset epileptic encephalopathies: from genotype to phenotype. Pediatr Neurol 46:24–31. McHugh PC, Rogers GR, Loudon B, Glubb DM, Joyce PR, Kennedy MA (2008) Proteomic analysis of embryonic stem cell-derived neural cells exposed to the antidepressant paroxetine. J Neurosci Res 86:306–316. Miyakawa T, Yared E, Pak JH, Huang FL, Huang KP, Crawley JN (2001) Neurogranin null mutant mice display performance deficits on spatial learning tasks with anxiety related components. Hippocampus 11:763–775. Morgan AR, Turic D, Jehu L, Hamilton G, Hollingworth P, Moskvina V, Jones L, Lovestone S, Brayne C, Rubinsztein DC, Lawlor B, Gill M, O’Donovan MC, Owen MJ, Williams J (2007) Association studies of 23 positional/functional candidate genes on chromosome 10 in late-onset Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet 144B:762–770. Novak G, Seeman P, Tallerico T (2006) Increased expression of calcium/calmodulin-dependent protein kinase IIbeta in frontal cortex in schizophrenia and depression. Synapse 59:61–68. Olah J, Vincze O, Virok D, Simon D, Bozso Z, Tokesi N, Horvath I, Hlavanda E, Kovacs J, Magyar A, Szucs M, Orosz F, Penke B, Ovadi J (2011) Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. J Biol Chem 286:34088–34100. Owada Y, Abdelwahab SA, Kitanaka N, Sakagami H, Takano H, Sugitani Y, Sugawara M, Kawashima H, Kiso Y, Mobarakeh JI, Yanai K, Kaneko K, Sasaki H, Kato H, SainoSaito S, Matsumoto N, Akaike N, Noda T, Kondo H (2006) Altered emotional behavioral responses in mice lacking brain-type fatty acid-binding protein gene. Eur J Neurosci 24:175–187. Park H, Kam TI, Kim Y, Choi H, Gwon Y, Kim C, Koh JY, Jung YK (2012) Neuropathogenic role of adenylate kinase-1 in Abeta-mediated tau phosphorylation via AMPK and GSK3beta. Hum Mol Genet 21:2725–2737. Park S, Jung SW, Kim BN, Cho SC, Shin MS, Kim JW, Yoo HJ, Cho DY, Chung US, Son JW, Kim HW (2013) Association between the GRM7 rs3792452 polymorphism and attention deficit hyperacitiveity disorder in a Korean sample. Behav Brain Funct 9:1. Pitts A, Dailey K, Newington JT, Chien A, Arseneault R, Cann T, Thompson LM, Cumming RC (2012) Dithiol-based compounds maintain expression of antioxidant protein peroxiredoxin 1 that counteracts toxicity of mutant huntingtin. J Biol Chem 287:22717–22729. Poduri A, Heinzen EL, Chitsazzadeh V, Lasorsa FM, Elhosary PC, LaCoursiere CM, Martin E, Yuskaitis CJ, Hill RS, Atabay KD, Barry B, Partlow JN, Bashiri FA, Zeidan RM, Elmalik SA, Kabiraj MM, Kothare S, Stodberg T, McTague A, Kurian MA, Scheffer IE, Barkovich AJ, Palmieri F, Salih MA, Walsh CA (2013) SLC25A22 is a novel gene for migrating partial seizures in infancy. Ann Neurol 74:873–882. Pomierny-Chamiolo L, Poleszak E, Pilc A, Nowak G (2010) NMDA but not AMPA glutamatergic receptors are involved in the antidepressant-like activity of MTEP during the forced swim test in mice. Pharmacol Rep 62:1186–1190. Reis SA, Thompson MN, Lee JM, Fossale E, Kim HH, Liao JK, Moskowitz MA, Shaw SY, Dong L, Haggarty SJ, MacDonald ME, Seong IS (2011) Striatal neurons expressing full-length mutant huntingtin exhibit decreased N-cadherin and altered neuritogenesis. Hum Mol Genet 20:2344–2355. Rippey C, Walsh T, Gulsuner S, Brodsky M, Nord AS, Gasperini M, Pierce S, Spurrell C, Coe BP, Krumm N, Lee MK, Sebat J, McClellan JM, King MC (2013) Formation of chimeric genes by copy-number variation as a mutational mechanism in schizophrenia. Am J Hum Genet 93:697–710. Saft C, Epplen JT, Wieczorek S, Landwehrmeyer GB, Roos RA, de Yebenes JG, Dose M, Tabrizi SJ, Craufurd D, Arning L (2011) NMDA receptor gene variations as modifiers in Huntington disease: a replication study. PLoS Curr 3:RRN1247. Saito S, Takahashi N, Ishihara R, Ikeda M, Suzuki T, Kitajima T, Yamanouchi Y, Iwata N, Yamada M, Yoshida K, Inada T, Ozaki N (2006) Association study between vesicleassociated membrane protein 2 gene polymorphisms and fluvoxamine response in Japanese major depressive patients. Neuropsychobiology 54:226–230. Sanchez-Mut JV, Aso E, Panayotis N, Lott I, Dierssen M, Rabano A, Urdinguio RG, Fernandez AF, Astudillo A, Martin-Subero JI, Balint B, Fraga MF, Gomez A, Gurnot C, Roux JC, Avila J, Hensch TK, Ferrer I, Esteller M (2013) DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease. Brain 136:3018– 3027. Schwindinger WF, Giger KE, Betz KS, Stauffer AM, Sunderlin EM, Sim-Selley LJ, Selley DE, Bronson SK, Robishaw JD (2004) Mice with deficiency of G protein gamma3 are lean and have seizures. Mol Cell Biol 24:7758–7768. Shan L, Bossers K, Unmehopa U, Bao AM, Swaab DF (2012) Alterations in the histaminergic system in Alzheimer’s disease: a postmortem study. Neurobiol Aging 33:2585– 2598.

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006

NSC 16186

No. of Pages 73

22 April 2015

X. Han et al. / Neuroscience xxx (2015) xxx–xxx

73

Shi J, Wang Q, Johansson JU, Liang X, Woodling NS, Priyam P, Loui TM, Merchant M, Breyer RM, Montine TJ, Andreasson K (2012) Inflammatory prostaglandin E2 signaling in a mouse model of Alzheimer disease. Ann Neurol 72:788–798. Shyn SI, Shi J, Kraft JB, Potash JB, Knowles JA, Weissman MM, Garriock HA, Yokoyama JS, McGrath PJ, Peters EJ, Scheftner WA, Coryell W, Lawson WB, Jancic D, Gejman PV, Sanders AR, Holmans P, Slager SL, Levinson DF, Hamilton SP (2011) Novel loci for major depression identified by genome-wide association study of Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three studies. Mol Psychiatry 16:202–215. Sillaber I, Panhuysen M, Henniger MS, Ohl F, Kuhne C, Putz B, Pohl T, Deussing JM, Paez-Pereda M, Holsboer F (2008) Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine. Psychopharmacology (Berl) 200:557–572. Soetanto A, Wilson RS, Talbot K, Un A, Schneider JA, Sobiesk M, Kelly J, Leurgans S, Bennett DA, Arnold SE (2010) Association of anxiety and depression with microtubuleassociated protein 2- and synaptopodin-immunolabeled dendrite and spine densities in hippocampal CA3 of older humans. Arch Gen Psychiatry 67:448–457. Su XW, Broach JR, Connor JR, Gerhard GS, Simmons Z (2014) Genetic heterogeneity of amyotrophic lateral sclerosis: implications for clinical practice and research. Muscle Nerve 49:786–803. Suszynska-Zajczyk J, Luczak M, Marczak L, Jakubowski H (2014) Hyperhomocysteinemia and bleomycin hydrolase modulate the expression of mouse brain proteins involved in neurodegeneration. J Alzheimers Dis 40:713–726. Tang J, Chen X, Xu X, Wu R, Zhao J, Hu Z, Xia K (2006) Significant linkage and association between a functional (GT)n polymorphism in promoter of the N-methyl-Daspartate receptor subunit gene (GRIN2A) and schizophrenia. Neurosci Lett 409:80–82. Thong JY, Qiu A, Sum MY, Kuswanto CN, Tuan TA, Donohoe G, Sitoh YY, Sim K (2013) Effects of the neurogranin variant rs12807809 on thalamocortical morphology in schizophrenia. PLoS One 8:e85603. Tsai SJ, Hong CJ, Liou YJ, Liao DL (2007) Association study of GOT2 genetic polymorphisms and schizophrenia. Psychiatr Genet 17:314. Turlington M, Malosh C, Jacobs J, Manka JT, Noetzel MJ, Vinson PN, Jadhav S, Herman EJ, Lavreysen H, Mackie C, Bartolome-Nebreda JM, Conde-Ceide S, Martin-Martin ML, Tong HM, Lopez S, MacDonald GJ, Steckler T, Daniels JS, Weaver CD, Niswender CM, Jones CK, Conn PJ, Lindsley CW, Stauffer SR (2014) Tetrahydronaphthyridine and dihydronaphthyridinone ethers as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu(5)). J Med Chem 57:5620–5637. Vaags AK, Bowdin S, Smith ML, Gilbert-Dussardier B, Brocke-Holmefjord KS, Sinopoli K, Gilles C, Haaland TB, Vincent-Delorme C, Lagrue E, Harbuz R, Walker S, Marshall CR, Houge G, Kalscheuer VM, Scherer SW, Minassian BA (2014) Absent CNKSR2 causes seizures and intellectual, attention, and language deficits. Ann Neurol 76:758– 764. Valdez SR, Patterson SI, Ezquer ME, Torrecilla M, Lama MC, Seltzer AM (2007) Acute sublethal global hypoxia induces transient increase of GAP-43 immunoreactivity in the striatum of neonatal rats. Synapse 61:124–137. Walton E, Geisler D, Hass J, Liu J, Turner J, Yendiki A, Smolka MN, Ho BC, Manoach DS, Gollub RL, Roessner V, Calhoun VD, Ehrlich S (2013) The impact of genome-wide supported schizophrenia risk variants in the neurogranin gene on brain structure and function. PLoS One 8:e76815. Weder N, Zhang H, Jensen K, Yang BZ, Simen A, Jackowski A, Lipschitz D, Douglas-Palumberi H, Ge M, Perepletchikova F, O’Loughlin K, Hudziak JJ, Gelernter J, Kaufman J (2014) Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry. J Am Acad Child Adolesc Psychiatry 53:417–424 e415. Wesseling H, Chan MK, Tsang TM, Ernst A, Peters F, Guest PC, Holmes E, Bahn S (2013) A combined metabonomic and proteomic approach identifies frontal cortex changes in a chronic phencyclidine rat model in relation to human schizophrenia brain pathology. Neuropsychopharmacology 38:2532–2544. Wilcoxon JS, Nadolski GJ, Samarut J, Chassande O, Redei EE (2007) Behavioral inhibition and impaired spatial learning and memory in hypothyroid mice lacking thyroid hormone receptor alpha. Behav Brain Res 177:109–116. Wright C, Turner JA, Calhoun VD, Perrone-Bizzozero N (2013) Potential Impact of miR-137 and Its Targets in Schizophrenia. Front Genet 4:58. Yoo MH, Gu X, Xu XM, Kim JY, Carlson BA, Patterson AD, Cai H, Gladyshev VN, Hatfield DL (2010) Delineating the role of glutathione peroxidase 4 in protecting cells against lipid hydroperoxide damage and in Alzheimer’s disease. Antioxid Redox Signal 12:819–827. Yu H, Bi W, Liu C, Zhao Y, Zhang JF, Zhang D, Yue W (2014) Protein-interaction-network-based analysis for genome-wide association analysis of schizophrenia in Han Chinese population. J Psychiatr Res 50:73–78. Zhao L, Li H, Guo R, Ma T, Hou R, Ma X, Du Y (2013) miR-137, a new target for post-stroke depression? Neural Regen Res 8:2441–2448.

973 974 975

(Accepted 2 April 2015) (Available online xxxx)

Please cite this article in press as: Han X et al. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2015.04.006