- Email: [email protected]
Chewing ameliorates stress-induced suppression of spatial memory by increasing glucocorticoid receptor expression in the hippocampus
BR A IN RE S E A RCH 1 4 46 ( 20 1 2 ) 3 4 –39
Available online at www.sciencedirect.com
www.elsevier.com/locate/brainres
Research Report
Chewing ameliorates stress-induced suppression of spatial memory by increasing glucocorticoid receptor expression in the hippocampus Shinjiro Miyakea,⁎, 1 , Gota Yoshikawaa, 1 , Kentaro Yamadab , Ken-ichi Sasaguria , Toshiharu Yamamotoc , Minoru Onozukab , Sadao Satoa a Department of Craniofacial Growth and Development Dentistry, Kanagawa Dental College, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan b Department of Physiology and Neuroscience, Kanagawa Dental College, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan c Department of Human Biology, Kanagawa Dental College, 82 Inaoka-cho Yokosuka Kanagawa, 238-8580, Japan
A R T I C LE I N FO
AB S T R A C T
Article history:
Chewing alters hypothalamic–pituitary–adrenal axis function and improves the ability to
Accepted 7 January 2012
cope with stress in rodents. Given that stress negatively influences hippocampus-
Available online 16 January 2012
dependent learning and memory, we aimed to elucidate whether masticatory movements, namely chewing, improve the stress-induced impairment of spatial memory in conjunction
Keywords:
with increased hippocampal glucocorticoid receptor expression. Male Sprague–Dawley rats
Chewing
were subjected to restraint stress by immobilization for 2 h: the stress with chewing (SC)
Spatial memory
group were allowed to chew on a wooden stick during the latter half of the immobilization
Water maze
period, whereas the stress without chewing (ST) group were not allowed to do so. Performance
Glucocorticoid receptor
in the Morris water maze test was significantly impaired in the ST group compared with the SC
HPA axis
group. Further, the numbers of glucocorticoid receptor immunopositive neurons in the hippo-
Immobilization stress
campal cornu ammonis 1 region were significantly lower in the ST group than in the control and SC groups. The control and SC rats showed no significant differences in both the water maze performance and the numbers of glucocorticoid receptor-immunopositive neurons. The immunohistochemical finding correlated with the performance in the water maze test. These results suggest that chewing is a behavioral mechanism to cope with stress by increasing hippocampal glucocorticoid receptor expression. © 2012 Elsevier B.V. All rights reserved.
⁎ Corresponding author. Fax: + 81 46 822 8885. E-mail address: [email protected] (S. Miyake). Abbreviations: HPA, hypothalamic-pituitary-adrenal; ACTH, adrenocorticotropic hormone; GR, glucocorticoid receptor; MWM, Morris water maze; ANOVA, analysis of variance; CT, control; ST, stress without chewing; SC, stress with chewing; SC, CA1, cornu ammonis 1; PBS, phosphate buffer containing saline; PBS-BSAT, PBS containing bovine serum albumin and Triton X-100; DAB, 3,3′-diaminobenzidine tetrahydrochloride 1 These authors contributed equally to the work. 0006-8993/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2012.01.011
BR A I N R ES E A RCH 1 4 46 ( 20 1 2 ) 3 4 –39
1.
35
Introduction
It has been reported that decreased masticatory function caused by the loss of molars, tooth attrition, or long-term intake of soft foods leads to impaired learning and memory processes and inhibits the negative-feedback response by the downregulation of GR protein and mRNA expression in the hippocampus (Ichihashi et al., 2007; Kubo et al., 2005; Onozuka et al., 1999, 2000, 2002; Tsutsui et al., 2007; Watanabe et al., 2001, 2002). The hippocampus is sensitive to stress and aging, and is one of the first regions to be structurally and functionally affected by severe and inescapable stress (McEwen, 2000). Stress stimulates the hypothalamic–pituitary–adrenal (HPA) axis and thereby causes the pituitary gland to secrete adrenocorticotropic hormone (ACTH). Elevated concentrations of this hormone, in turn, cause the adrenal cortex to secrete corticosterone. The hippocampus is a target region of corticosterone, and an elevated concentration of corticosterone suppresses hippocampus-dependent learning and memory (Bodnoff et al., 1995; de Kloet et al., 1998; Diamond et al., 2004; Kim and Diamond, 2002; Kim et al., 2006; Woodson et al., 2003). The hippocampus has two types of adrenal steroid receptors: Type I (mineralocorticoid receptor) and Type II (glucocorticoid receptor, GR). They play important roles in the HPA axis through their effects on glucocorticoid negative feedback (Herman et al., 1989). The direct and principal mechanism by which glucocorticoids inhibit the HPA axis by negative feedback is through the inhibition of both the hypothalamus and the hypophysis. The indirect negative feedback mechanism of the HPA axis reduces the secretion of glucocorticoids by their binding to GRs in the hippocampus (Sapolsky et al., 1984). Chronic secretion of glucocorticoids stimulated by chronic stress downregulates GR protein and mRNA levels in the hippocampus (Freeman et al., 2004; Herman et al., 1995; Sapolsky et al., 1984, 1986). Previous reports suggest that masticatory movements reduce the negative influence of stress on hippocampaldependent memory. For example, chewing ameliorates the stress-induced impairment of N-methyl-D-aspartate receptor-mediated long-term potentiation (Ono et al., 2008). Further, activation of the histamine H1 receptor by chewing, mediates the recovery of stress-suppressed hippocampal synaptic plasticity (Ono et al., 2009). The aim of this study was to elucidate whether chewing improves stress-induced suppression of spatial memory in conjunction with increased hippocampal GR expression. We hypothesized that chewing improves stress-induced spatial memory performance in Morris water maze tasks and increases the GR protein level in hippocampus.
2.
Results
2.1.
Spatial learning
In the hippocampus-dependent hidden platform version of the MWM task, all groups exhibited significantly short latencies to find the hidden platform during the 32 training trials
Fig. 1 – Spatial learning in the MWM test. The results represent the mean score ± SEM (n= 9, 7, and 8 rats in the CT, ST, and SC groups, respectively) of four trials per block.
over four consecutive days (4trials/block, 2 blocks/day). The rate of acquisition was comparable among the groups (repeated measures two-way analysis of variance [ANOVA]; group × day interaction: F (2, 21) = 0.73, P > 0.05; main effect of group: F (2, 21) = 3.31, P > 0.05; main effect of day: F (2, 21) = 53.0, P < 0.05) (Fig. 1).
2.2.
Spatial memory
In the spatial memory test 24 h after the immobilization and chewing condition, the stress without chewing (ST) group (30.0 ± 4.3 s, n = 7) exhibited significantly longer latencies to swim to the original location of the platform than the control (CT) group (11.5 ± 2.1 s, n = 9) and the stress with chewing (SC) group (16.3 ± 4.3 s, n = 8) (one-way ANOVA: F (2, 21) = 6.78, P < 0.01; post hoc Tukey–Kramer test: P < 0.01 for ST group vs. CT group, P < 0.05 for ST group vs. SC group). The CT and SC groups showed no significant difference (Fig. 2).
2.3.
GR immunopositivity
Photomicrographs showed GR induction in the cornu ammonis 1 (CA1) regions of all the groups after the spatial memory test. Further, GR-specific immunostaining was observed in the hippocampus of all the animals examined (Fig. 3).
Fig. 2 – Effect of chewing on impaired memory caused by restraint stress. The results represent the mean score SEM (n = 9, 7, and 8 rats in the CT, ST, and SC groups, respectively). *P < 0.05, **P < 0.01.
36
BR A IN RE S E A RCH 1 4 46 ( 20 1 2 ) 3 4 –39
Fig. 3 – Photomicrographs of GR-immunopositive cells in the hippocampal formation (A–C) and CA1 subfields (a–c) after the special memory test in the MWM.
2.4. Correlation between the special memory and the GR immunopositivity
GR-positive cells/mm square
Correlation analysis indicated a statistically significant inverse correlation between the goal in time in spatial memory
**
350
**
300 250 200 150 100 50
test and the number of GR immunopositive cells in the ST and the SC groups (Spearman Rho = −0.83, P = 0.001, n = 7; 8 rats in the ST and SC groups, respectively) (Fig. 5).
3.
Discussion
In this study, we provide evidence that chewing improves stress suppressed hippocampus-dependent spatial memory. In the present experiments, the ST rats, exposed to 2 h
GR-positive cells/mm square
However, the number of GR-immunopositive cells in the ST group (194 ± 6.1, n = 7) was significantly lower than that in the CT group (264 ± 6.27, n = 9) and SC group (285 ± 5.46, n = 8) (one-way ANOVA: F (2, 21) = 57.2, P < 0.01; post hoc Tukey–Kramer test: P < 0.01 for ST group vs. CT group, ST group vs. SC group). Again, no significant difference was observed between the CT and the SC groups (Fig. 4).
350 300 250 200 150 100 ST
50 0
SC
0
5
10
15
20
25
30
35
40
45
50
Goal in time (s)
0 CT
ST
SC
Fig. 4 – Effect of chewing on the number of GRimmunopositive neurons in the hippocampus after restraint stress. The results represent the mean number of neurons/ mm2 ± SEM (n = 9, 7, and 8 rats in the CT, ST, and SC groups, respectively). *P < 0.05, **P < 0.01.
Fig. 5 – Correlation between the spatial memory and the GRimmunopositivity. Scatterplot showing the correlation between the goal in time in the special memory test and the number of GR-immunopositive cells. The solid line indicates the Spearman Rho correlation (rs = − 0.83, P = 0.001; n = 7 and 8 rats in the ST and SC groups, respectively).
BR A I N R ES E A RCH 1 4 46 ( 20 1 2 ) 3 4 –39
restraint stress without chewing, had impaired memory related performance in the MWM tests relative to the SC rats, exposed to 2 h restraint stress with chewing. In a previous study using a similar condition, 2 h restraint stress significantly increased the ACTH and corticosterone levels in stressed rats, but chewing for the latter half of the 2 h stress period significantly decreased both these levels (Lee et al., 2008). Previous research showed that stress can affect spatial learning and memory processes by increasing the plasma concentration of corticosterone and influencing hippocampal long-term potentiation and hippocampus-dependent behavior in the MWM tests (Diamond and Rose, 1994; Diamond et al., 1992, 1994; Foy et al., 1987; Joëls and Krugers, 2007; Kim and Yoon, 1998; Kim et al., 1996, 2001, 2005; Mesches et al., 1999; Shors et al., 1990). Our findings are therefore consistent with the extended literature the effects of stress on memory performance. Several recent studies have suggested that chewing of a wooden stick during restraint stress rescues the stressimpaired hippocampal functions (Ono et al., 2008, 2009). Restraint stress induces the expression of corticotrophinreleasing hormone in the paraventricular nucleus of the rat hypothalamus (Givalois et al., 2004), whereas chewing during restrain stress significantly suppresses the stress-induced enhancement of corticotrophin-releasing hormone expression in the paraventricular nucleus (Hori et al., 2004). Together with our data, these findings suggest that stress produces spatial memory deficits via HPA axis dysregulation but chewing prevents these deficits We also found that chewing increases the number of stress-suppressed GR-immunopositive neurons in the hippocampal CA1 areas 24 h after restraint stress. In the present study, the ST rats showed significantly decreased GR expression in the CA1 region compared with the CT rats, but chewing significantly increased the GR expression in this region. This finding could be related to the better performance of the SC rats in the spatial memory trial, because GRs play an important role in memory consolidation and retrieval (de Kloet et al., 1999; Oitzl and de Kloet, 1992; Oitzl et al., 2001). Neuroendocrinal activation of the HPA axis is counteracted by GR-mediated negative feedback, which terminates the stress response. However, decreased masticatory function inhibits the negative-feedback response by downregulation of GR protein and mRNA expression (Ichihashi et al., 2007). Although previous researchers have shown that increased GR protein levels in the hippocampus are associated with increased negative-feedback sensitivity to glucocorticoids and the subsequent dampened neuroendocrinal response to stress (Meaney et al., 1985, 1989, 1992, 1996; O'Donnell et al., 1994; Stamatakis et al., 2008), the present study is the first demonstration that chewing increases the GR protein levels in the hippocampus. We emphasize that the masticatory activation plays an effective role in the maintenance of hippocampus-dependent memory processes under severe stress conditions. However, there is no consensus regarding the relevant neuronal and humoral pathways from the oral cavity to the hippocampus. The neuronal pathways by which mastication directly and indirectly influences the HPA axis should be clarified in future studies.
37
In conclusion, the present results support our hypothesis that chewing is a behavioral skill to cope with stress.
4.
Experimental procedure
4.1.
Animals
Male Sprague–Dawley rats aged 10 weeks (Nihon SLC, Shizuoka, Japan) and weighing 300–330 g were used. The rats were group-housed (4/cage) in a room maintained under controlled light conditions (12:12 h light: dark cycle) and temperature (22 ± 3 °C). They had free access to food pellets and tap water. The experimental protocol was reviewed and approved by the Committee on Ethics on Animal Experiments of Kanagawa Dental College and the Guidelines for Animal Experimentation of Kanagawa Dental College were adhered to.
4.2.
Spatial learning experiment
In the MWM the animals were required to find a platform submerged (1 cm below the water level) in a circular pool of opaque water by using only distal spatial cues available within the testing room. The pool (180 cm in diameter) was filled with water (23–26 °C) rendered opaque by floating granules of styrene foam (~2 mm in diameter). The platform was hidden near the center of one of the four quadrants of the pool. Each animal was subjected to 32 trials over 4 consecutive days (4 trials/block, 2 blocks/day). The starting point was randomly distributed across the four quadrants. The rats were required to find the hidden platform within 60 s. If a rat failed to find the platform within this timeframe, it was manually guided to and allowed to stay on the platform. At the end of each trial, the rat was left on the platform for 20 s and then was placed in a holding cage for 40 s before the next trial. The rat's behavior was monitored with a closed-circuit device video camera linked to a computer system (Top Scan, CleverSys, Inc., Reston, VA).
4.3.
Immobilization and chewing condition
Immediately after the last training trial in the MWM, 24 animals were divided into CT, ST, and SC groups to equalize the rate of acquisition in the MWM task that they had undergone. The CT rats were not immobilized, but the ST and SC rats were immobilized to produce acute stress according to a wellestablished protocol (Hori et al., 2004, 2005). Restraint stress was induced by securing each rat to a wooden board (18 cm × 25 cm) in the supine position by using a leather belt, and all four legs were fixed at 45° to the body midline with adhesive tape. The ST rats were maintained in this position for 2 h, whereas the SC rats were allowed to chew a wooden stick during the latter half of the immobilization period.
4.4.
Spatial memory experiment
Twenty-four hours after immobilization and chewing conditions, the hidden platform in the MWM task was removed from the pool. The rats were placed on the opposite side of the target area in the pool and allowed to follow the trail for
38
BR A IN RE S E A RCH 1 4 46 ( 20 1 2 ) 3 4 –39
60 s. Their movements and the time taken to reach the position at which the platform had been located in the training trials were monitored by using automated behavioral analysis software (TopScan).
4.5.
Immunohistochemistry
Ninety minutes after the spatial memory test, animals were deeply anesthetized with pentobarbital sodium (Wako Pure Chemical Industries, Ltd., Osaka, Japan). They were then perfused with 8% paraformaldehyde, 0.1 M lysine, and 0.01 M NaIO4. Their brains were rapidly dissected and fixed in the same fixative for 1 or 2 days at 4 °C. After washing in phosphate buffer and immersing in 20% sucrose, the specimens were cut into 20-μm-thick transverse sections by using a sliding microtome equipped with a freezing stage, and freefloating sections were immunostained. Immunohistochemical analysis was performed mainly according to our routine method (Yamamoto et al., 1997). In brief, the sections were washed overnight in 0.1 M phosphate buffer (pH 7.4) containing 0.9% saline (PBS) and incubated with rabbit polyclonal antibody against GR (Abcam, San Francisco, CA; 1:100) in PBS containing 1% bovine serum albumin and 0.3% Triton X-100 (PBS-BSAT) for 24 h at 4 °C. After washing in PBS, the sections were incubated with secondary antibody (biotinylated anti-rabbit IgG) diluted 1:100 in PBS-BSAT for 1 h at room temperature. They were then washed again in PBS and incubated with avidin–biotin–horseradish peroxidase complex (ABC; Vector Laboratories, Burlingame, CA) diluted 1:100 in PBS-BSAT for 30 min at room temperature. After the final wash in PBS, the sections were reacted with 0.02% 3,3′-diaminobenzidine tetrahydrochloride (DAB) and 0.005% hydrogen peroxide in 0.05 M Tris-HCI buffer (pH 7.4). Thereafter, the sections were placed on coverslips with Malinol (Muto Pure Chemicals, Tokyo, Japan). Some sections were mounted without counterstaining.
4.6.
Cell counting
The anatomical position of the sliced brain sections was determined according to the rat brain map (Paxinos and Watson, 1986). GR-immunopositive neurons in the CA1 region were manually counted under a light microscope (Nikon, Tokyo, Japan). Cell counting was performed independently and blindly by two investigators (Stamatakis et al., 2008). The total number of GR-immunopositive neurons on only one side of the CA1 region was calculated, because similar numbers of GRimmunopositive neurons were evident on both sides of the CA1 regions. GR-immunopositive cells in the hippocampus (between 3.30 and −3.60 mm from the bregma) were counted in six sections per animal by using a 20× microscope objective. In each section, all labeled cells were counted on a stratum pyramidale length (diagonal of a 300-μm2 area) in each zone.
4.7.
Statistical analysis
The data are expressed as the mean ± SEM. The effects of the learning trials were assessed by repeated-measures two-way ANOVA. When an interaction between independent factors was detected, post hoc Tukey–Kramer test was used to
identify specific differences among the groups. The data of the spatial memory test and immunohistochemical study were assessed by one-way ANOVA and post hoc Tukey–Kramer test. The Spearman Rho value was used to explore correlation between the goal in time in spatial memory test and the number of GR-immunopositve cells. All differences were considered statistically significant at P < 0.05.
Acknowledgments The study was performed at the Research Institute of Occlusion Medicine and Research Center of Brain and Oral Science, Kanagawa Dental College, and was supported by a Grant-inAid for Open Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, and a Grantin-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.
REFERENCES
Bodnoff, S.R., Humphreys, A.G., Lehman, J.C., Diamond, D.M., Rose, G.M., Meaney, M.J., 1995. Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-age rats. J. Neurosci. 15, 61–69. de Kloet, E.R., Vreugdenhil, E., Oitzl, M.S., Joëls, M., 1998. Brain corticosteroid receptor balance in health and disease. Endocr. Rev. 19, 269–301. de Kloet, E.R., Oitzl, M.S., Joëls, M., 1999. Stress and cognition: are corticosteroids good or bad guys? Trends Neurosci. 22, 422–426. Diamond, D.M., Rose, G.M., 1994. Stress impairs LTP and hippocampal-dependent memory. Ann. N. Y. Acad. Sci. 746, 411–414. Diamond, D.M., Bennett, M.C., Fleshner, M., Rose, G.M., 1992. Inverted-U relationship between the level of peripheral corticosterone and the magnitude of hippocampal primed burst potentiation. Hippocampus 2, 421–430. Diamond, D.M., Fleshner, M., Rose, G.M., 1994. Psychological stress repeatedly blocks hippocampal primed burst potentiation in behaving rats. Behav. Brain Res. 62, 1–9. Diamond, D.M., Park, C.R., Woodson, J.C., 2004. Stress generates emotional memories and retrograde amnesia by inducing an endogenous from of hippocampal LTP. Hippocampus 14, 281–291. Foy, M.R., Stanton, M.E., Levine, S., Thompson, R.F., 1987. Behavioral stress impairs long-term potentiation in rodent hippocampus. Behav. Neural Biol. 48, 138–149. Freeman, A.I., Munn, H.L., Lyons, V., Dammermann, A., Seckl, J.R., Chapman, K.E., 2004. Glucocorticoid down-regulation of rat glucocorticoid receptor does not involve differential promoter regulation. J. Endocrinol. 183, 365–374. Givalois, L., Naert, G., Rage, F., Ixart, G., Arancibia, S., TapiaArancibia, L., 2004. A single brain-derived neurotrophic factor injection modifies hypothalamo–pituitary–adenocortical axis activity in adult male rats. Mol. Cell. Neurosci. 27, 280–295. Herman, J.P., Patel, P.D., Akil, H., Watson, S.J., 1989. Localization and regulation of glucocorticoid and mineralocorticoid receptor messenger RNAs in the hippocampal formation of the rat. Mol. Endocrinol. 3, 1886–1894. Herman, J.P., Adams, D., Prewitt, C., 1995. Regulatory changes in neuroendocrine stress-integrative circuitry produced by a variable stress paradigm. Neuroendocrinology 61, 180–190.
BR A I N R ES E A RCH 1 4 46 ( 20 1 2 ) 3 4 –39
Hori, N., Yuyama, N., Tamura, K., 2004. Biting suppresses stressinduced expression of corticotropin-releasing factor (CRF) in the rat hypothalamus. J. Dent. Res. 83, 124–128. Hori, N., Lee, M.C., Sasaguri, K., Ishii, H., Kamei, M., Kimoto, K., Toyoda, M., Sato, S., 2005. Suppression of stress-induced nNOS expression in the rat hypothalamus by biting. J. Dent. Res. 84, 624–628. Ichihashi, Y., Arakawa, Y., Iinuma, M., Tamura, Y., Kubo, K., Iwaku, F., Sato, Y., Onozuka, M., 2007. Occlusal disharmony attenuates glucocorticoid negative feedback in aged SAMP8 mice. Neurosci. Lett. 427, 71–76. Joëls, M., Krugers, H.J., 2007. LTP after stress: up or down? Neural Plast. 2007, 93–202. Kim, J.J., Diamond, D.M., 2002. The stressed hippocampus, synaptic plasticity and lost memory. Nat. Rev. Neurosci. 3, 453–462. Kim, J.J., Yoon, K.S., 1998. Stress: metaplastic effects in the hippocampus. Trends Neurosci. 21, 505–509. Kim, J.J., Foy, M.R., Thompson, R.F., 1996. Behavioral stress modifies hippocampal plasticity through N-methyl- D-aspartate receptor activation. Proc. Natl. Acad. Sci. U. S. A. 93, 4750–4753. Kim, J.J., Lee, H.J., Han, J.S., Packard, M.G., 2001. Amygdala is critical for stress-induced modulation of hippocampal longterm potentiation and learning. J. Neurosci. 21, 5222–5228. Kim, J.J., Koo, J.W., Lee, H.J., Han, J.S., 2005. Amygdalar inactivation blocks stress-induced impairments in hippocampal long-term potentiation and spatial memory. J. Neurosci. 25, 1532–1539. Kim, J.J., Song, E.Y., Kosten, T.A., 2006. Stress effects in the hippocampus: synaptic plasticity and memory. Stress 9, 1–11. Kubo, K.Y., Iwaku, F., Watanabe, K., Fujita, M., Onozuka, M., 2005. Molarless-induced changes of spines in hippocampal region of SAMP8 mice. Brain Res. 1057, 191–195. Lee, T., Saruta, J., Sasaguri, K., Sato, S., Tsukinoki, K., 2008. Allowing animals to bite reverses the effects of immobilization stress on hippocampal neurotrophin expression. Brain Res. 1195, 43–49. McEwen, B.S., 2000. The neurobiology of stress: from serendipity to clinical relevance. Brain Res. 886, 172–189. Meaney, M.J., Aitken, D.H., Bodnoff, S.R., Iny, L.J., Tatarewicz, J.E., Spolsky, R.M., 1985. Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions. Behav. Neurosci. 99, 765–770. Meaney, M.J., Aitken, D.H., Viau, V., Sharma, S., Sarrieau, A., 1989. Neonatal handling alters adrenocortical negative feedback sensitivity and hippocampal type II glucocorticoid receptor binding in the rat. Neuroendocrinology 50, 597–604. Meaney, M.J., Aitken, D.H., Sharma, S., Viau, V., 1992. Basal ACTH, corticosterone and corticosterone-binding globulin levels over the diurnal cycle, and age-related changes in hippocampal type I and type II corticosteroid receptor binding capacity in young and aged, handled and nonhandled rats. Neuroendocrinology 55, 204–213. Meaney, M.J., Diorio, J., Francis, D., Widdowson, J., LaPlante, P., Caldji, C., Sharma, S., Seckl, J.R., Plotsky, P.M., 1996. Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress. Dev. Neurosci. 18, 49–72. Mesches, M.H., Fleshner, M., Heman, K.L., Rose, G.M., Diamond, D.M., 1999. Exposing rats to a predator blocks primed burst potentiation in the hippocampus in vitro. J. Neurosci. 19, RC18. O'Donnell, D., Larocque, S., Seckl, J.R., Meaney, M.J., 1994. Postnatal handling alters glucocorticoid, but not mineralocorticoid messenger RNA expression in the hippocampus of adult rats. Brain Res. Mol. Brain Res. 26, 242–248.
39
Oitzl, M.S., de Kloet, E.R., 1992. Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning. Behav. Neurosci. 106, 62–71. Oitzl, M.S., Rechardt, H.M., Joëls, M., de Kloet, E.R., 2001. Point mutation in the mouse glucocorticoid receptor preventing DNA binding impairs spatial memory. Proc. Natl. Acad. Sci. U. S. A. 98, 12790–12795. Ono, Y., Kataoka, T., Miyake, S., Cheng, S.-J., Tachibana, A., Sasaguri, K.-I., Onozuka, M., 2008. Chewing ameliorates stressinduced suppression of hippocampal long-term potentiation. Neuroscience 154, 1352–1359. Ono, Y., Kataoka, T., Miyake, S., Sasaguri, K., Sato, S., Onozuka, M., 2009. Chewing rescues stress-suppressed hippocampal longterm potentiation via activation of histamine H1 receptor. Neurosci. Res. 64, 385–390. Onozuka, M., Watanabe, K., Mirbod, S.M., Ozono, S., Nishiyama, K., Karasawa, N., Nagatsu, I., 1999. Reduced mastication stimulates impairment of spatial memory and degeneration of hippocampal neurons in age SAMP8 mice. Brain Res. 826, 148–153. Onozuka, M., Watanabe, K., Nagasaki, S., Jiang, Y., Ozono, S., Nishiyama, K., Kawase, T., Karasawa, N., Nagatsu, I., 2000. Impairment of spatial memory and changes in astroglial responsiveness following loss of molar teeth in aged SAMP8 mice. Behav. Brain Res. 108, 145–155. Onozuka, M., Watanabe, K., Fujita, M., Tonosaki, K., Saito, S., 2002. Evidence for involvement of glucocorticoid response in the hippocampal changes in aged molarless SAMP8 mice. Behav. Brain Res. 131, 125–129. Paxinos, G., Watson, C., 1986. The Rat Brain in Stereotaxic Coordinates, 2nd ed. Academic Press, New York. Sapolsky, R.M., Krey, B.S., McEwen, B.S., 1984. Stress downregulates corticosterone receptors in a site-specific manner in the brain. Endocrinology 114, 287–292. Sapolsky, R.M., Krey, L.C., McEwen, B.S., 1986. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr. Rev. 7, 284–301. Shors, T.J., Foy, M.R., Levine, S., Thompson, R.F., 1990. Unpredictable and uncontrollable stress impairs neuronal plasticity in the rat hippocampal. Brain Res. Bull. 24, 663–667. Stamatakis, A., Pondiki, S., Kitraki, E., Diamantopoulou, A., Panagiotaropoulos, T., Raftogianni, A., Stylianopoulou, F., 2008. Effect of neonatal handling on adult rat spatial learning and memory following acute stress. Stress 11, 148–159. Tsutsui, K., Kaku, M., Motokawa, M., Tohma, Y., Kawata, T., Fujita, T., Kohno, S., Ohtani, J., Tenjoh, K., Nakano, M., Kamada, H., Tanne, K., 2007. Influences of reduced masticatory sensory input from soft-diet feeding upon spatial memory/learning ability in mice. Biomed. Res. 28, 1–7. Watanabe, K., Tonosaki, K., Kawase, T., Karasawa, N., Nagatsu, I., Fujita, M., Onozuka, M., 2001. Evidence for involvement of dysfunctional teeth in the senile process in the hippocampus of SAMP8 mice. Exp. Gerontol. 36, 283–295. Watanabe, K., Ozono, S., Nishiyama, K., Saito, S., Tonosaki, K., Fujita, M., Onozuka, M., 2002. The molarless condition in aged SAMP8 mice attenuates hippocampal Fos induction linked to water maze performance. Behav. Brain Res. 128, 19–25. Woodson, J.C., Macintosh, D., Fleshner, M., Diamond, D.M., 2003. Emotioninduced amnesia in rat: working memory-specific impairment, corticosterone-memory correlation, and fear versus arousal effects on memory. Learn. Mem. 10, 326–336. Yamamoto, T., Suzuki, H., Uemura, H., 1997. Endothelin B receptor-like immunoreactivity is associated with LHRHimmunoreactive fibers in the rat hypothalamus. Neurosci. Lett. 223, 117–120.
Available online at www.sciencedirect.com
www.elsevier.com/locate/brainres
Research Report
Chewing ameliorates stress-induced suppression of spatial memory by increasing glucocorticoid receptor expression in the hippocampus Shinjiro Miyakea,⁎, 1 , Gota Yoshikawaa, 1 , Kentaro Yamadab , Ken-ichi Sasaguria , Toshiharu Yamamotoc , Minoru Onozukab , Sadao Satoa a Department of Craniofacial Growth and Development Dentistry, Kanagawa Dental College, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan b Department of Physiology and Neuroscience, Kanagawa Dental College, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan c Department of Human Biology, Kanagawa Dental College, 82 Inaoka-cho Yokosuka Kanagawa, 238-8580, Japan
A R T I C LE I N FO
AB S T R A C T
Article history:
Chewing alters hypothalamic–pituitary–adrenal axis function and improves the ability to
Accepted 7 January 2012
cope with stress in rodents. Given that stress negatively influences hippocampus-
Available online 16 January 2012
dependent learning and memory, we aimed to elucidate whether masticatory movements, namely chewing, improve the stress-induced impairment of spatial memory in conjunction
Keywords:
with increased hippocampal glucocorticoid receptor expression. Male Sprague–Dawley rats
Chewing
were subjected to restraint stress by immobilization for 2 h: the stress with chewing (SC)
Spatial memory
group were allowed to chew on a wooden stick during the latter half of the immobilization
Water maze
period, whereas the stress without chewing (ST) group were not allowed to do so. Performance
Glucocorticoid receptor
in the Morris water maze test was significantly impaired in the ST group compared with the SC
HPA axis
group. Further, the numbers of glucocorticoid receptor immunopositive neurons in the hippo-
Immobilization stress
campal cornu ammonis 1 region were significantly lower in the ST group than in the control and SC groups. The control and SC rats showed no significant differences in both the water maze performance and the numbers of glucocorticoid receptor-immunopositive neurons. The immunohistochemical finding correlated with the performance in the water maze test. These results suggest that chewing is a behavioral mechanism to cope with stress by increasing hippocampal glucocorticoid receptor expression. © 2012 Elsevier B.V. All rights reserved.
⁎ Corresponding author. Fax: + 81 46 822 8885. E-mail address: [email protected] (S. Miyake). Abbreviations: HPA, hypothalamic-pituitary-adrenal; ACTH, adrenocorticotropic hormone; GR, glucocorticoid receptor; MWM, Morris water maze; ANOVA, analysis of variance; CT, control; ST, stress without chewing; SC, stress with chewing; SC, CA1, cornu ammonis 1; PBS, phosphate buffer containing saline; PBS-BSAT, PBS containing bovine serum albumin and Triton X-100; DAB, 3,3′-diaminobenzidine tetrahydrochloride 1 These authors contributed equally to the work. 0006-8993/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2012.01.011
BR A I N R ES E A RCH 1 4 46 ( 20 1 2 ) 3 4 –39
1.
35
Introduction
It has been reported that decreased masticatory function caused by the loss of molars, tooth attrition, or long-term intake of soft foods leads to impaired learning and memory processes and inhibits the negative-feedback response by the downregulation of GR protein and mRNA expression in the hippocampus (Ichihashi et al., 2007; Kubo et al., 2005; Onozuka et al., 1999, 2000, 2002; Tsutsui et al., 2007; Watanabe et al., 2001, 2002). The hippocampus is sensitive to stress and aging, and is one of the first regions to be structurally and functionally affected by severe and inescapable stress (McEwen, 2000). Stress stimulates the hypothalamic–pituitary–adrenal (HPA) axis and thereby causes the pituitary gland to secrete adrenocorticotropic hormone (ACTH). Elevated concentrations of this hormone, in turn, cause the adrenal cortex to secrete corticosterone. The hippocampus is a target region of corticosterone, and an elevated concentration of corticosterone suppresses hippocampus-dependent learning and memory (Bodnoff et al., 1995; de Kloet et al., 1998; Diamond et al., 2004; Kim and Diamond, 2002; Kim et al., 2006; Woodson et al., 2003). The hippocampus has two types of adrenal steroid receptors: Type I (mineralocorticoid receptor) and Type II (glucocorticoid receptor, GR). They play important roles in the HPA axis through their effects on glucocorticoid negative feedback (Herman et al., 1989). The direct and principal mechanism by which glucocorticoids inhibit the HPA axis by negative feedback is through the inhibition of both the hypothalamus and the hypophysis. The indirect negative feedback mechanism of the HPA axis reduces the secretion of glucocorticoids by their binding to GRs in the hippocampus (Sapolsky et al., 1984). Chronic secretion of glucocorticoids stimulated by chronic stress downregulates GR protein and mRNA levels in the hippocampus (Freeman et al., 2004; Herman et al., 1995; Sapolsky et al., 1984, 1986). Previous reports suggest that masticatory movements reduce the negative influence of stress on hippocampaldependent memory. For example, chewing ameliorates the stress-induced impairment of N-methyl-D-aspartate receptor-mediated long-term potentiation (Ono et al., 2008). Further, activation of the histamine H1 receptor by chewing, mediates the recovery of stress-suppressed hippocampal synaptic plasticity (Ono et al., 2009). The aim of this study was to elucidate whether chewing improves stress-induced suppression of spatial memory in conjunction with increased hippocampal GR expression. We hypothesized that chewing improves stress-induced spatial memory performance in Morris water maze tasks and increases the GR protein level in hippocampus.
2.
Results
2.1.
Spatial learning
In the hippocampus-dependent hidden platform version of the MWM task, all groups exhibited significantly short latencies to find the hidden platform during the 32 training trials
Fig. 1 – Spatial learning in the MWM test. The results represent the mean score ± SEM (n= 9, 7, and 8 rats in the CT, ST, and SC groups, respectively) of four trials per block.
over four consecutive days (4trials/block, 2 blocks/day). The rate of acquisition was comparable among the groups (repeated measures two-way analysis of variance [ANOVA]; group × day interaction: F (2, 21) = 0.73, P > 0.05; main effect of group: F (2, 21) = 3.31, P > 0.05; main effect of day: F (2, 21) = 53.0, P < 0.05) (Fig. 1).
2.2.
Spatial memory
In the spatial memory test 24 h after the immobilization and chewing condition, the stress without chewing (ST) group (30.0 ± 4.3 s, n = 7) exhibited significantly longer latencies to swim to the original location of the platform than the control (CT) group (11.5 ± 2.1 s, n = 9) and the stress with chewing (SC) group (16.3 ± 4.3 s, n = 8) (one-way ANOVA: F (2, 21) = 6.78, P < 0.01; post hoc Tukey–Kramer test: P < 0.01 for ST group vs. CT group, P < 0.05 for ST group vs. SC group). The CT and SC groups showed no significant difference (Fig. 2).
2.3.
GR immunopositivity
Photomicrographs showed GR induction in the cornu ammonis 1 (CA1) regions of all the groups after the spatial memory test. Further, GR-specific immunostaining was observed in the hippocampus of all the animals examined (Fig. 3).
Fig. 2 – Effect of chewing on impaired memory caused by restraint stress. The results represent the mean score SEM (n = 9, 7, and 8 rats in the CT, ST, and SC groups, respectively). *P < 0.05, **P < 0.01.
36
BR A IN RE S E A RCH 1 4 46 ( 20 1 2 ) 3 4 –39
Fig. 3 – Photomicrographs of GR-immunopositive cells in the hippocampal formation (A–C) and CA1 subfields (a–c) after the special memory test in the MWM.
2.4. Correlation between the special memory and the GR immunopositivity
GR-positive cells/mm square
Correlation analysis indicated a statistically significant inverse correlation between the goal in time in spatial memory
**
350
**
300 250 200 150 100 50
test and the number of GR immunopositive cells in the ST and the SC groups (Spearman Rho = −0.83, P = 0.001, n = 7; 8 rats in the ST and SC groups, respectively) (Fig. 5).
3.
Discussion
In this study, we provide evidence that chewing improves stress suppressed hippocampus-dependent spatial memory. In the present experiments, the ST rats, exposed to 2 h
GR-positive cells/mm square
However, the number of GR-immunopositive cells in the ST group (194 ± 6.1, n = 7) was significantly lower than that in the CT group (264 ± 6.27, n = 9) and SC group (285 ± 5.46, n = 8) (one-way ANOVA: F (2, 21) = 57.2, P < 0.01; post hoc Tukey–Kramer test: P < 0.01 for ST group vs. CT group, ST group vs. SC group). Again, no significant difference was observed between the CT and the SC groups (Fig. 4).
350 300 250 200 150 100 ST
50 0
SC
0
5
10
15
20
25
30
35
40
45
50
Goal in time (s)
0 CT
ST
SC
Fig. 4 – Effect of chewing on the number of GRimmunopositive neurons in the hippocampus after restraint stress. The results represent the mean number of neurons/ mm2 ± SEM (n = 9, 7, and 8 rats in the CT, ST, and SC groups, respectively). *P < 0.05, **P < 0.01.
Fig. 5 – Correlation between the spatial memory and the GRimmunopositivity. Scatterplot showing the correlation between the goal in time in the special memory test and the number of GR-immunopositive cells. The solid line indicates the Spearman Rho correlation (rs = − 0.83, P = 0.001; n = 7 and 8 rats in the ST and SC groups, respectively).
BR A I N R ES E A RCH 1 4 46 ( 20 1 2 ) 3 4 –39
restraint stress without chewing, had impaired memory related performance in the MWM tests relative to the SC rats, exposed to 2 h restraint stress with chewing. In a previous study using a similar condition, 2 h restraint stress significantly increased the ACTH and corticosterone levels in stressed rats, but chewing for the latter half of the 2 h stress period significantly decreased both these levels (Lee et al., 2008). Previous research showed that stress can affect spatial learning and memory processes by increasing the plasma concentration of corticosterone and influencing hippocampal long-term potentiation and hippocampus-dependent behavior in the MWM tests (Diamond and Rose, 1994; Diamond et al., 1992, 1994; Foy et al., 1987; Joëls and Krugers, 2007; Kim and Yoon, 1998; Kim et al., 1996, 2001, 2005; Mesches et al., 1999; Shors et al., 1990). Our findings are therefore consistent with the extended literature the effects of stress on memory performance. Several recent studies have suggested that chewing of a wooden stick during restraint stress rescues the stressimpaired hippocampal functions (Ono et al., 2008, 2009). Restraint stress induces the expression of corticotrophinreleasing hormone in the paraventricular nucleus of the rat hypothalamus (Givalois et al., 2004), whereas chewing during restrain stress significantly suppresses the stress-induced enhancement of corticotrophin-releasing hormone expression in the paraventricular nucleus (Hori et al., 2004). Together with our data, these findings suggest that stress produces spatial memory deficits via HPA axis dysregulation but chewing prevents these deficits We also found that chewing increases the number of stress-suppressed GR-immunopositive neurons in the hippocampal CA1 areas 24 h after restraint stress. In the present study, the ST rats showed significantly decreased GR expression in the CA1 region compared with the CT rats, but chewing significantly increased the GR expression in this region. This finding could be related to the better performance of the SC rats in the spatial memory trial, because GRs play an important role in memory consolidation and retrieval (de Kloet et al., 1999; Oitzl and de Kloet, 1992; Oitzl et al., 2001). Neuroendocrinal activation of the HPA axis is counteracted by GR-mediated negative feedback, which terminates the stress response. However, decreased masticatory function inhibits the negative-feedback response by downregulation of GR protein and mRNA expression (Ichihashi et al., 2007). Although previous researchers have shown that increased GR protein levels in the hippocampus are associated with increased negative-feedback sensitivity to glucocorticoids and the subsequent dampened neuroendocrinal response to stress (Meaney et al., 1985, 1989, 1992, 1996; O'Donnell et al., 1994; Stamatakis et al., 2008), the present study is the first demonstration that chewing increases the GR protein levels in the hippocampus. We emphasize that the masticatory activation plays an effective role in the maintenance of hippocampus-dependent memory processes under severe stress conditions. However, there is no consensus regarding the relevant neuronal and humoral pathways from the oral cavity to the hippocampus. The neuronal pathways by which mastication directly and indirectly influences the HPA axis should be clarified in future studies.
37
In conclusion, the present results support our hypothesis that chewing is a behavioral skill to cope with stress.
4.
Experimental procedure
4.1.
Animals
Male Sprague–Dawley rats aged 10 weeks (Nihon SLC, Shizuoka, Japan) and weighing 300–330 g were used. The rats were group-housed (4/cage) in a room maintained under controlled light conditions (12:12 h light: dark cycle) and temperature (22 ± 3 °C). They had free access to food pellets and tap water. The experimental protocol was reviewed and approved by the Committee on Ethics on Animal Experiments of Kanagawa Dental College and the Guidelines for Animal Experimentation of Kanagawa Dental College were adhered to.
4.2.
Spatial learning experiment
In the MWM the animals were required to find a platform submerged (1 cm below the water level) in a circular pool of opaque water by using only distal spatial cues available within the testing room. The pool (180 cm in diameter) was filled with water (23–26 °C) rendered opaque by floating granules of styrene foam (~2 mm in diameter). The platform was hidden near the center of one of the four quadrants of the pool. Each animal was subjected to 32 trials over 4 consecutive days (4 trials/block, 2 blocks/day). The starting point was randomly distributed across the four quadrants. The rats were required to find the hidden platform within 60 s. If a rat failed to find the platform within this timeframe, it was manually guided to and allowed to stay on the platform. At the end of each trial, the rat was left on the platform for 20 s and then was placed in a holding cage for 40 s before the next trial. The rat's behavior was monitored with a closed-circuit device video camera linked to a computer system (Top Scan, CleverSys, Inc., Reston, VA).
4.3.
Immobilization and chewing condition
Immediately after the last training trial in the MWM, 24 animals were divided into CT, ST, and SC groups to equalize the rate of acquisition in the MWM task that they had undergone. The CT rats were not immobilized, but the ST and SC rats were immobilized to produce acute stress according to a wellestablished protocol (Hori et al., 2004, 2005). Restraint stress was induced by securing each rat to a wooden board (18 cm × 25 cm) in the supine position by using a leather belt, and all four legs were fixed at 45° to the body midline with adhesive tape. The ST rats were maintained in this position for 2 h, whereas the SC rats were allowed to chew a wooden stick during the latter half of the immobilization period.
4.4.
Spatial memory experiment
Twenty-four hours after immobilization and chewing conditions, the hidden platform in the MWM task was removed from the pool. The rats were placed on the opposite side of the target area in the pool and allowed to follow the trail for
38
BR A IN RE S E A RCH 1 4 46 ( 20 1 2 ) 3 4 –39
60 s. Their movements and the time taken to reach the position at which the platform had been located in the training trials were monitored by using automated behavioral analysis software (TopScan).
4.5.
Immunohistochemistry
Ninety minutes after the spatial memory test, animals were deeply anesthetized with pentobarbital sodium (Wako Pure Chemical Industries, Ltd., Osaka, Japan). They were then perfused with 8% paraformaldehyde, 0.1 M lysine, and 0.01 M NaIO4. Their brains were rapidly dissected and fixed in the same fixative for 1 or 2 days at 4 °C. After washing in phosphate buffer and immersing in 20% sucrose, the specimens were cut into 20-μm-thick transverse sections by using a sliding microtome equipped with a freezing stage, and freefloating sections were immunostained. Immunohistochemical analysis was performed mainly according to our routine method (Yamamoto et al., 1997). In brief, the sections were washed overnight in 0.1 M phosphate buffer (pH 7.4) containing 0.9% saline (PBS) and incubated with rabbit polyclonal antibody against GR (Abcam, San Francisco, CA; 1:100) in PBS containing 1% bovine serum albumin and 0.3% Triton X-100 (PBS-BSAT) for 24 h at 4 °C. After washing in PBS, the sections were incubated with secondary antibody (biotinylated anti-rabbit IgG) diluted 1:100 in PBS-BSAT for 1 h at room temperature. They were then washed again in PBS and incubated with avidin–biotin–horseradish peroxidase complex (ABC; Vector Laboratories, Burlingame, CA) diluted 1:100 in PBS-BSAT for 30 min at room temperature. After the final wash in PBS, the sections were reacted with 0.02% 3,3′-diaminobenzidine tetrahydrochloride (DAB) and 0.005% hydrogen peroxide in 0.05 M Tris-HCI buffer (pH 7.4). Thereafter, the sections were placed on coverslips with Malinol (Muto Pure Chemicals, Tokyo, Japan). Some sections were mounted without counterstaining.
4.6.
Cell counting
The anatomical position of the sliced brain sections was determined according to the rat brain map (Paxinos and Watson, 1986). GR-immunopositive neurons in the CA1 region were manually counted under a light microscope (Nikon, Tokyo, Japan). Cell counting was performed independently and blindly by two investigators (Stamatakis et al., 2008). The total number of GR-immunopositive neurons on only one side of the CA1 region was calculated, because similar numbers of GRimmunopositive neurons were evident on both sides of the CA1 regions. GR-immunopositive cells in the hippocampus (between 3.30 and −3.60 mm from the bregma) were counted in six sections per animal by using a 20× microscope objective. In each section, all labeled cells were counted on a stratum pyramidale length (diagonal of a 300-μm2 area) in each zone.
4.7.
Statistical analysis
The data are expressed as the mean ± SEM. The effects of the learning trials were assessed by repeated-measures two-way ANOVA. When an interaction between independent factors was detected, post hoc Tukey–Kramer test was used to
identify specific differences among the groups. The data of the spatial memory test and immunohistochemical study were assessed by one-way ANOVA and post hoc Tukey–Kramer test. The Spearman Rho value was used to explore correlation between the goal in time in spatial memory test and the number of GR-immunopositve cells. All differences were considered statistically significant at P < 0.05.
Acknowledgments The study was performed at the Research Institute of Occlusion Medicine and Research Center of Brain and Oral Science, Kanagawa Dental College, and was supported by a Grant-inAid for Open Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, and a Grantin-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.
REFERENCES
Bodnoff, S.R., Humphreys, A.G., Lehman, J.C., Diamond, D.M., Rose, G.M., Meaney, M.J., 1995. Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-age rats. J. Neurosci. 15, 61–69. de Kloet, E.R., Vreugdenhil, E., Oitzl, M.S., Joëls, M., 1998. Brain corticosteroid receptor balance in health and disease. Endocr. Rev. 19, 269–301. de Kloet, E.R., Oitzl, M.S., Joëls, M., 1999. Stress and cognition: are corticosteroids good or bad guys? Trends Neurosci. 22, 422–426. Diamond, D.M., Rose, G.M., 1994. Stress impairs LTP and hippocampal-dependent memory. Ann. N. Y. Acad. Sci. 746, 411–414. Diamond, D.M., Bennett, M.C., Fleshner, M., Rose, G.M., 1992. Inverted-U relationship between the level of peripheral corticosterone and the magnitude of hippocampal primed burst potentiation. Hippocampus 2, 421–430. Diamond, D.M., Fleshner, M., Rose, G.M., 1994. Psychological stress repeatedly blocks hippocampal primed burst potentiation in behaving rats. Behav. Brain Res. 62, 1–9. Diamond, D.M., Park, C.R., Woodson, J.C., 2004. Stress generates emotional memories and retrograde amnesia by inducing an endogenous from of hippocampal LTP. Hippocampus 14, 281–291. Foy, M.R., Stanton, M.E., Levine, S., Thompson, R.F., 1987. Behavioral stress impairs long-term potentiation in rodent hippocampus. Behav. Neural Biol. 48, 138–149. Freeman, A.I., Munn, H.L., Lyons, V., Dammermann, A., Seckl, J.R., Chapman, K.E., 2004. Glucocorticoid down-regulation of rat glucocorticoid receptor does not involve differential promoter regulation. J. Endocrinol. 183, 365–374. Givalois, L., Naert, G., Rage, F., Ixart, G., Arancibia, S., TapiaArancibia, L., 2004. A single brain-derived neurotrophic factor injection modifies hypothalamo–pituitary–adenocortical axis activity in adult male rats. Mol. Cell. Neurosci. 27, 280–295. Herman, J.P., Patel, P.D., Akil, H., Watson, S.J., 1989. Localization and regulation of glucocorticoid and mineralocorticoid receptor messenger RNAs in the hippocampal formation of the rat. Mol. Endocrinol. 3, 1886–1894. Herman, J.P., Adams, D., Prewitt, C., 1995. Regulatory changes in neuroendocrine stress-integrative circuitry produced by a variable stress paradigm. Neuroendocrinology 61, 180–190.
BR A I N R ES E A RCH 1 4 46 ( 20 1 2 ) 3 4 –39
Hori, N., Yuyama, N., Tamura, K., 2004. Biting suppresses stressinduced expression of corticotropin-releasing factor (CRF) in the rat hypothalamus. J. Dent. Res. 83, 124–128. Hori, N., Lee, M.C., Sasaguri, K., Ishii, H., Kamei, M., Kimoto, K., Toyoda, M., Sato, S., 2005. Suppression of stress-induced nNOS expression in the rat hypothalamus by biting. J. Dent. Res. 84, 624–628. Ichihashi, Y., Arakawa, Y., Iinuma, M., Tamura, Y., Kubo, K., Iwaku, F., Sato, Y., Onozuka, M., 2007. Occlusal disharmony attenuates glucocorticoid negative feedback in aged SAMP8 mice. Neurosci. Lett. 427, 71–76. Joëls, M., Krugers, H.J., 2007. LTP after stress: up or down? Neural Plast. 2007, 93–202. Kim, J.J., Diamond, D.M., 2002. The stressed hippocampus, synaptic plasticity and lost memory. Nat. Rev. Neurosci. 3, 453–462. Kim, J.J., Yoon, K.S., 1998. Stress: metaplastic effects in the hippocampus. Trends Neurosci. 21, 505–509. Kim, J.J., Foy, M.R., Thompson, R.F., 1996. Behavioral stress modifies hippocampal plasticity through N-methyl- D-aspartate receptor activation. Proc. Natl. Acad. Sci. U. S. A. 93, 4750–4753. Kim, J.J., Lee, H.J., Han, J.S., Packard, M.G., 2001. Amygdala is critical for stress-induced modulation of hippocampal longterm potentiation and learning. J. Neurosci. 21, 5222–5228. Kim, J.J., Koo, J.W., Lee, H.J., Han, J.S., 2005. Amygdalar inactivation blocks stress-induced impairments in hippocampal long-term potentiation and spatial memory. J. Neurosci. 25, 1532–1539. Kim, J.J., Song, E.Y., Kosten, T.A., 2006. Stress effects in the hippocampus: synaptic plasticity and memory. Stress 9, 1–11. Kubo, K.Y., Iwaku, F., Watanabe, K., Fujita, M., Onozuka, M., 2005. Molarless-induced changes of spines in hippocampal region of SAMP8 mice. Brain Res. 1057, 191–195. Lee, T., Saruta, J., Sasaguri, K., Sato, S., Tsukinoki, K., 2008. Allowing animals to bite reverses the effects of immobilization stress on hippocampal neurotrophin expression. Brain Res. 1195, 43–49. McEwen, B.S., 2000. The neurobiology of stress: from serendipity to clinical relevance. Brain Res. 886, 172–189. Meaney, M.J., Aitken, D.H., Bodnoff, S.R., Iny, L.J., Tatarewicz, J.E., Spolsky, R.M., 1985. Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions. Behav. Neurosci. 99, 765–770. Meaney, M.J., Aitken, D.H., Viau, V., Sharma, S., Sarrieau, A., 1989. Neonatal handling alters adrenocortical negative feedback sensitivity and hippocampal type II glucocorticoid receptor binding in the rat. Neuroendocrinology 50, 597–604. Meaney, M.J., Aitken, D.H., Sharma, S., Viau, V., 1992. Basal ACTH, corticosterone and corticosterone-binding globulin levels over the diurnal cycle, and age-related changes in hippocampal type I and type II corticosteroid receptor binding capacity in young and aged, handled and nonhandled rats. Neuroendocrinology 55, 204–213. Meaney, M.J., Diorio, J., Francis, D., Widdowson, J., LaPlante, P., Caldji, C., Sharma, S., Seckl, J.R., Plotsky, P.M., 1996. Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress. Dev. Neurosci. 18, 49–72. Mesches, M.H., Fleshner, M., Heman, K.L., Rose, G.M., Diamond, D.M., 1999. Exposing rats to a predator blocks primed burst potentiation in the hippocampus in vitro. J. Neurosci. 19, RC18. O'Donnell, D., Larocque, S., Seckl, J.R., Meaney, M.J., 1994. Postnatal handling alters glucocorticoid, but not mineralocorticoid messenger RNA expression in the hippocampus of adult rats. Brain Res. Mol. Brain Res. 26, 242–248.
39
Oitzl, M.S., de Kloet, E.R., 1992. Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning. Behav. Neurosci. 106, 62–71. Oitzl, M.S., Rechardt, H.M., Joëls, M., de Kloet, E.R., 2001. Point mutation in the mouse glucocorticoid receptor preventing DNA binding impairs spatial memory. Proc. Natl. Acad. Sci. U. S. A. 98, 12790–12795. Ono, Y., Kataoka, T., Miyake, S., Cheng, S.-J., Tachibana, A., Sasaguri, K.-I., Onozuka, M., 2008. Chewing ameliorates stressinduced suppression of hippocampal long-term potentiation. Neuroscience 154, 1352–1359. Ono, Y., Kataoka, T., Miyake, S., Sasaguri, K., Sato, S., Onozuka, M., 2009. Chewing rescues stress-suppressed hippocampal longterm potentiation via activation of histamine H1 receptor. Neurosci. Res. 64, 385–390. Onozuka, M., Watanabe, K., Mirbod, S.M., Ozono, S., Nishiyama, K., Karasawa, N., Nagatsu, I., 1999. Reduced mastication stimulates impairment of spatial memory and degeneration of hippocampal neurons in age SAMP8 mice. Brain Res. 826, 148–153. Onozuka, M., Watanabe, K., Nagasaki, S., Jiang, Y., Ozono, S., Nishiyama, K., Kawase, T., Karasawa, N., Nagatsu, I., 2000. Impairment of spatial memory and changes in astroglial responsiveness following loss of molar teeth in aged SAMP8 mice. Behav. Brain Res. 108, 145–155. Onozuka, M., Watanabe, K., Fujita, M., Tonosaki, K., Saito, S., 2002. Evidence for involvement of glucocorticoid response in the hippocampal changes in aged molarless SAMP8 mice. Behav. Brain Res. 131, 125–129. Paxinos, G., Watson, C., 1986. The Rat Brain in Stereotaxic Coordinates, 2nd ed. Academic Press, New York. Sapolsky, R.M., Krey, B.S., McEwen, B.S., 1984. Stress downregulates corticosterone receptors in a site-specific manner in the brain. Endocrinology 114, 287–292. Sapolsky, R.M., Krey, L.C., McEwen, B.S., 1986. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr. Rev. 7, 284–301. Shors, T.J., Foy, M.R., Levine, S., Thompson, R.F., 1990. Unpredictable and uncontrollable stress impairs neuronal plasticity in the rat hippocampal. Brain Res. Bull. 24, 663–667. Stamatakis, A., Pondiki, S., Kitraki, E., Diamantopoulou, A., Panagiotaropoulos, T., Raftogianni, A., Stylianopoulou, F., 2008. Effect of neonatal handling on adult rat spatial learning and memory following acute stress. Stress 11, 148–159. Tsutsui, K., Kaku, M., Motokawa, M., Tohma, Y., Kawata, T., Fujita, T., Kohno, S., Ohtani, J., Tenjoh, K., Nakano, M., Kamada, H., Tanne, K., 2007. Influences of reduced masticatory sensory input from soft-diet feeding upon spatial memory/learning ability in mice. Biomed. Res. 28, 1–7. Watanabe, K., Tonosaki, K., Kawase, T., Karasawa, N., Nagatsu, I., Fujita, M., Onozuka, M., 2001. Evidence for involvement of dysfunctional teeth in the senile process in the hippocampus of SAMP8 mice. Exp. Gerontol. 36, 283–295. Watanabe, K., Ozono, S., Nishiyama, K., Saito, S., Tonosaki, K., Fujita, M., Onozuka, M., 2002. The molarless condition in aged SAMP8 mice attenuates hippocampal Fos induction linked to water maze performance. Behav. Brain Res. 128, 19–25. Woodson, J.C., Macintosh, D., Fleshner, M., Diamond, D.M., 2003. Emotioninduced amnesia in rat: working memory-specific impairment, corticosterone-memory correlation, and fear versus arousal effects on memory. Learn. Mem. 10, 326–336. Yamamoto, T., Suzuki, H., Uemura, H., 1997. Endothelin B receptor-like immunoreactivity is associated with LHRHimmunoreactive fibers in the rat hypothalamus. Neurosci. Lett. 223, 117–120.