e30
Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1–e52
vaccine experimental inflammation model together with computational modelling of an instrumental learning task performed during fMRI (1). Twenty-two healthy participants were each tested 3-h after blindly administered typhoid vaccine (0.025 mg) and placebo (0.5 ml 0.9% NaCl) injection. Typhoid but not placebo was associated with a threefold increase in plasma IL-6 (t(21) = 5.20, p < 0.001) confirming induction of mild inflammation. Following inflammation participants demonstrated greater avoidance of a punishing cue (loss £1) and significantly reduced selection of a rewarded cue F(21,1) = 6.41, p = 0.019. Computational modelling of individuals’ choices using a Q-learning model (free parameters alpha (learningrate), beta (choice-randomness) and R (reward value)) demonstrated significant reduction in reward cue value and increase in value of punishment cues following inflammation F(21,1) = 3.63, p < 0.05. fMRI confirmed previous correlations of appetitive and aversive prediction error (PE) within ventral striatal (VS) and anterior insula (AI) regions of interest respectively (FWE p < 0.05) across conditions. However, inflammation significantly impaired VS responses to appetitive PE and enhanced AI responses to aversive PE (FWE p < 0.05) suggesting that inflammation modulates the value of aversive and appetitive cues via actions on VS and AI prediction error signals respectively. (1) Pessiglione et al., 2006. Nature 442, 1042–45. http://dx.doi.org/10.1016/j.bbi.2014.06.121
102. Enriched maternal care decreases opioid self-administration in adulthood and alters neuroimmune signaling in the nucleus accumbens M.J. Lacagnina a, G.M. Houtz a, C. Wells b, S. Slade b, E.D. Levin b, S.D. Bilbo a a
Duke University, Department of Psychology and Neuroscience, 210 Research Drive, Durham, NC 27708, USA b Duke University Medical Center, USA Despite decades of progress, the biological mechanisms underlying addiction are unknown. Glia, including astrocytes and microglia, profoundly influence neuronal function and may play a critical role in the development of drug addiction. Previously, we have shown that a neonatal handling procedure (which promotes enriched maternal care) reduces glial activation to an acute morphine challenge and prevents reinstatement of morphine conditioned place preference; likewise, similar results were obtained by pharmacological manipulation of glia within the nucleus accumbens (NAc). Here, we investigated the effects of opioid self-administration on central immune signaling within the NAc and its modulation by early-life experience. Male rat pups were handled (15 min/day) from postnatal day (P) 2 to P20 or left undisturbed. In adulthood, all rats were tested for self-administration of intravenous remifentanil (a short-acting opioid) in daily 1 h sessions for 2 weeks. Brains were then collected to examine persistent alterations in glial activation. Neonatal handling reduced acquisition of remifentanil; this effect was specific for opioids, as acquisition of food reward was unaffected. Remifentanil self-administration substantially increased glial antigen expression (Iba1 and GFAP) and proinflammatory gene expression in NAc, including the innate immune receptor TLR4. However, only handled rats showed increased expression of the anti-inflammatory cytokine IL-10. These data establish neural–glial interactions in the NAc as an essential component of self-motivated drug acquisition that can be altered by early-life environmental conditions. http://dx.doi.org/10.1016/j.bbi.2014.06.122
103. Maternal perinatal high-fat diet increases anxiety-like behavior in male offspring G. Winther a, S. Lund b, H.K. Müller a, G. Wegener a a
Translational Neuropsychiatric Unit, Department of Clinical Medicine, Skovagervej 2, Aarhus University, Riiskov, Aarhus 8240, Denmark b Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 9 Nørrebrogade 44, Bldg. 3.0, 8000 Aarhus C, Denmark Background: Maternal obesity during gestation represents a significant health risk for the offspring, becoming evident later in life and includes metabolic syndrome, cardiovascular disease and affective disorders. Inflammation has recently been shown to play an important role in the pathophysiology of affective disorders. Systemic inflammation is a hallmark consequence of a high-fat diet and maternal obesity may lead to fetal inflammatory responses. Objective: The aim of this study was to investigate the influence of a high-fat diet on the affective-like behavior in the offspring. Methods: Age matched female rats (Sprague Dawley, n = 20) were fed a high-fat diet or a control diet 8 weeks before breeding, and continued on this diet throughout gestation and lactation. Offspring were weaned onto normal diet. Male and female offspring were tested at the age of PND56 in different behavioral settings for anxiety- (Elevated plus-maze) and depression-like (Forced swim test) behavior. Insulin sensitivity was evaluated using the oral glucose tolerance test (OGTT). Results: Offspring from high fat fed rats were significantly heavier than control offspring at weaning. Male offspring exposed to perinatal high-fat showed increased anxiety-like behavior. There was no significant difference in the depression-like behavior in males or females. Conclusion: The data suggest that dietary environment during development, has behavioral consequences. This effect seems to be specific for anxiety. http://dx.doi.org/10.1016/j.bbi.2014.06.123
104. Overcrowding stress decreases macrophage activity and increases Salmonella Enteritidis invasion in broiler chickens J. Palermo-Neto a, W.M. Quinteiro-Filho a, A. Ribeiro a, V. Ferraz-de-Paula a, E. Baskeville a, M.L. Pinheiro a, A.T. Akamine a, C.S. Astolfi-Ferreira b, A.J. Ferreira b, A.V. Gomes b a
Neuroimmunomodulation Research Group, Department of Pathology, School of Veterinary Medicine, University of São Paulo, São Paulo, Brazil b Laboratory of Ornitopathology, School of Veterinary Medicine, University of São Paulo, São Paulo, SP, Brazil Overcrowding stress is a reality in the poultry industry. Chickens exposed to long-term stressful situations present a reduction of welfare and immunosuppression. We designed this experiment to analyze the effects of overcrowding stress (16 birds/m2) on performance parameters, serum corticosterone levels, the relative weight of the bursa of Fabricius, plasma IgA and IgG levels, intestinal integrity, macrophage activity and experimental Salmonella Enteritidis invasion. The overcrowding stress decreased performance parameters, induced enteritis and decreased macrophage activity and the relative bursa weight in broiler chickens. When the chickens were similarly stressed and infected with Salmonella Enteritidis, there was an increase in feed conversion and a decrease in plasma IgG levels in the stressed and Salmonella-infected birds. Moderate enteritis was observed throughout the duodenum of chickens stressed and infected with Salmonella. Moreover, the overcrowding stress decreased the macrophage phagocytosis intensity and increased Salmonella Enteritidis counts in the livers of birds challenged with
Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1–e52
the pathogenic bacterium. Thus, we believe that overcrowding stress via the hypothalamic–pituitary–adrenal axis that is associated with an increase in corticosterone and enteritis might influence the quality of the intestinal immune barrier and the integrity of the small intestine. This effect allowed pathogenic bacteria to migrate through the intestinal mucosa, resulted in inflammatory infiltration and Salmonella invasion. http://dx.doi.org/10.1016/j.bbi.2014.06.124
105. Enhanced glucocorticoid sensitivity coupled with reduced microglial activation in a genetically predisposed animal model of depression E. Sherwin a,b, S. Gormley a, B. McGuinness a,b, A. Harkin a
e31
(CBF) in cortical and limbic regions of the brain as measured by bolus tracking Arterial Spin Labelling (bt-ASL) when compared to the Wistar strain. Male Wistar and WKY rats (200–250 g, n = 7–10 per group) were subjected to a series of behavioural tests referred to above to establish the behavioural phenotype. MR-btASL scans were undertaken in a 7-Tesla Bruker BioSpec 70/30 magnet system. The WKY strain exhibits a significant decrease in CBF measures in prefrontal cortical (PFC) regions relative to WIS controls. A significant negative correlation was found between MRI perfusion parameters and GFAP positive cell number in the PFC of WKY but not Wistar rats. These data suggest that changes in GFAP positive cell number in the WKY rat model may be associated with changes in resting state CBF in the frontal cortex. http://dx.doi.org/10.1016/j.bbi.2014.06.126
a
Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland b School of Medicine, Ireland The Wistar-Kyoto (WKY) rat exhibits a genetic predisposition to a stress-sensitive depression-related phenotype. The aim of this investigation was to assess stress-related glucocorticoid sensitivity and immune responses in the strain so as to elucidate putative neuroimmune interactions. Circulating corticosterone concentrations were lower in WKY rats relative to the comparator Wistar strain at baseline but increased in both strains in response to stress. Both WKY and Wistar strains exhibited a stress-related increase in the expression of the glucocorticoid-inducible genes GILZ, SGK1 and p11 in the brain (frontal cortex, hippocampus and hypothalamus), the response being greater in the WKY strain. GR expression was suppressed in response to stress in the WKY strain only. Similarly, expression of the monocyte/microglial markers, CD-11B and CD74, were attenuated in the WKY relative to the Wistar strain following stress exposure. This was observed in tandem with a stress-related increase in IL-6 expression in the WKY rat only. Both strains exhibited a stress-related increase in the expression of FKBP5 and TDO in the liver, the response being greater in the WKY rat. Measurement of hepatic TDO activity revealed that conversion of tryptophan to kynurenine was greater in the WKY rat relative to Wistar controls following stress exposure indicative of kynurenine pathway induction. The observed interaction between the stress-induced endocrine and immune axes may account for the depressive-related phenotype characteristic of this strain. http://dx.doi.org/10.1016/j.bbi.2014.06.125
106. Reduced cortical astroglial cell numbers coupled to reduced cortical cerebral blood perfusion in a genetically predisposed model of depression as assessed by magnetic resonance bolus tracking arterial spin labelling (MR-btASL) S. Gormley a,b, C. Kerskens a, A. Harkin a,b a Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Dublin D2, Ireland b School of Pharmacy and Pharmaceutical Sciences, Ireland
The inbred Wistar-Kyoto (WKY) rat is a putative animal model of depression previously reported to exhibit decreased cell numbers immunoreactive for astroglial cell marker glial fibrillary acidic protein (GFAP). The WKY strain exhibit a depressive and anxiety like phenotype across the range of behavioural paradigms including the FST, EPM, OF and light/dark box relative to other rat strains including the Wistar background strain. We sought to investigate if WKY rats displayed any differences in regional cerebral blood flow
107. CD8+ T cells are important for recovery from chemotherapy-induced neuropathy in mice K. Krukowski a, N. Eijkelkamp b, H. Wang b, M. Qi-Lang a,c, R. Dantzer a, C.J. Heijnen a,b, A. Kavelaars a,b a
University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA b University Medical Center Utrecht, Netherlands c Fudan University, China Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting toxicity for cancer treatment. In this study we investigated the contribution of T cells in the course of CIPN. Wild type (WT; C57Bl6J) and T cell-deficient mice (Rag1 / ) were treated with chemotherapy (paclitaxel) and mechanical hyperalgesia was measured. Mechanical hyperalgesia developed immediately following treatment in WT and Rag1 / mice. In WT mice paclitaxelinduced mechanical hyperalgesia resolved 14 days after treatment. However, in Rag1 / mice mechanical hyperalgesia persisted for more than 21 days. When T cells (CD3+) were transferred into Rag1 / mice paclitaxel-induced mechanical hyperalgesia resolved by 14 days. These data demonstrate that T cells are critical for resolution from CIPN. Paclitaxel administration has been shown to damage peripheral sensory neuron cell bodies located in dorsal root ganglia (DRGs). Immunohistochemistry analysis revealed that the transferred T cells localized to (DRGs) in Rag1 / mice. Next, we investigated if a single T cell subset was responsible for resolution from CIPN. Transfer of CD8+ T cells into Rag1 / mice was sufficient to normalize resolution of paclitaxel-induced mechanical hyperalgesia by 14 days. In contrast when Rag1 / mice were injected with CD4+ T cells mechanical hyperalgesia persisted for up to 21 days. How CD8+ T cells regulate resolution from CIPN is under investigation, nevertheless this is the first study to our knowledge to identify a beneficial role for CD8+ T cells in CIPN. http://dx.doi.org/10.1016/j.bbi.2014.06.127
108. Peri-adolescent high fructose diet remodels the hypothalamic transcriptome and increases hypothalamic and hippocampal complement gene expression C.S. Harrell a, Z.P. Johnson b,c, G.N. Neigh a,d a
Department of Physiology, Emory University, 615 Michael Street, Suite 675, Atlanta, GA 30307, USA b Yerkes National Primate Center, Emory University, USA c Nonhuman Primate Genomics Lab, Emory University, USA d Department of Psychiatry and Behavioral Sciences, Emory University, USA