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Research Article | Open Access

Glucocorticoid receptor, a potential mediator of differential regulation on amygdala neurons by chronic stress

Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang 330031, China
School of Life Sciences, Nanchang University, Nanchang 330031, China
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Abstract

The amygdala, a key target for chronic stress, forms the hub of the brain’s emotional circuits with the medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC). The structural and functional remodeling of the amygdala, especially the basolateral amygdala (BLA), caused by chronic stress is closely related to attendant changes in mood disorders such as anxiety disorders. Our previous study found that chronic stress differentially regulated BLA projection neurons (PNs) in different circuits, as evidenced by the fact that spine density and glutamatergic signaling only in BLA PNs targeting vHPC (BLA→vHPC PNs) were remodeled by chronic restraint stress (CRS), whereas BLA PNs targeting mPFC (BLA→mPFC PNs) and nucleus accumbens (BLA→NAc PNs) were not markedly altered. However, the underlying mechanisms are unclear. These BLA PNs integrated in different neural circuits are in an almost-the-same microenvironment, but triggered different reactions to stress, suggesting that they may have different signal receiving or transmitting mechanisms. Considering the critical role of glucocorticoids in the modulation of brain structure and function by stress, we hypothesize that glucocorticoid receptor (GR) may be a potential mediator of the differential regulation of BLA neurons by chronic stress. In this study, we sought to clarify whether the expression levels of GR on BLA PNs in different circuits and their response patterns to CRS are different. And the results showed that CRS significantly enhanced the GR expression of BLA→vHPC PNs, but had no obvious effect on the GR expression of BLA→mPFC PNs and BLA→NAc PNs. Moreover, the increase of corticosterone concentration in mice caused by prolonged stress only selectively caused the elevated response of GR in BLA→vHPC PNs. Taken together, our findings hint that the GR may be a potential and essential mediator of chronic stress-caused differential regulation on BLA PN.

References

[1]
de Kloet, E. R., Joëls, M., Holsboer, F. Stress and the brain: From adaptation to disease. Nature Reviews Neuroscience, 2005, 6(6): 463475.
[2]
McEwen, B. S., Bowles, N. P., Gray, J. D., Hill, M. N., Hunter, R. G., Karatsoreos, I. N. Nasca, C. Mechanisms of stress in the brain. Nature Neuroscience, 2015, 18(10): 13531363.
[3]
Kim, P., Evans, G. W., Angstadt, M., Ho, S. S., Sripada, C. S., Swain, J. E., Liberzon, I., Phan, K. L. Effects of childhood poverty and chronic stress on emotion regulatory brain function in adulthood. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(46): 1844218447.
[4]
Lupien, S. J., Juster, R. P., Raymond, C., Marin, M. F. The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity. Frontiers in Neuroendocrinology, 2018, 49: 91105.
[5]
Roozendaal, B., McEwen, B. S., Chattarji, S. Stress, memory and the amygdala. Nature Reviews Neuroscience, 2009, 10(6): 423433.
[6]
Ressler, K. J. Amygdala activity, fear, and anxiety: Modulation by stress. Biological Psychiatry, 2010, 67(12): 11171119.
[7]
Bryant, R. A., Kemp, A. H., Felmingham, K. L., Liddell, B., Olivieri, G., Peduto, A., Gordon, E., Williams, L. M. Enhanced amygdala and medial prefrontal activation during nonconscious processing of fear in posttraumatic stress disorder: An fMRI study. Human Brain Mapping, 2008, 29(5): 517523.
[8]
Andrewes, D. G., Jenkins, L. M. The role of the amygdala and the ventromedial prefrontal cortex in emotional regulation: Implications for post-traumatic stress disorder. Neuropsychology Review, 2019, 29(2): 220243.
[9]
Vyas, A., Mitra, R., Shankaranarayana Rao, B. S., Chattarji, S. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. The Journal of Neuroscience, 2002, 22(15): 68106818.
[10]
Colyn, L., Venzala, E., Marco, S., Perez-Otaño, I., Tordera, R. M. Chronic social defeat stress induces sustained synaptic structural changes in the prefrontal cortex and amygdala. Behav Brain Res, 2019, 373: 112079.
[11]
Liu, W. Z., Zhang, W. H., Zheng, Z. H., Zou, J. X., Liu, X. X., Huang, S. H., You, W. J., He, Y., Zhang, J. Y., Wang, X. D. et al. Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety. Nature Communications, 2020, 11(1): 2221.
[12]
McEwen, B. S., Nasca, C., Gray, J. D. Stress effects on neuronal structure: Hippocampus, amygdala, and prefrontal cortex. Neuropsychopharmacology, 2016, 41(1): 323.
[13]
Cook, S. C., Wellman, C. L. Chronic stress alters dendritic morphology in rat medial prefrontal cortex. Journal of Neurobiology, 2004, 60(2): 236248.
[14]
McEwen, B. S., Milner, T. A. Hippocampal formation: Shedding light on the influence of sex and stress on the brain. Brain Res Rev, 2007, 55(2): 343355.
[15]
Zhang, W. H., Zhang, J. Y., Holmes, A., Pan, B. X. Amygdala circuit substrates for stress adaptation and adversity. Biological Psychiatry, 2021, 89(9): 847856.
[16]
Ozawa, M., Davis, P., Ni, J., Maguire, J., Papouin, T., Reijmers, L. Experience-dependent resonance in amygdalo-cortical circuits supports fear memory retrieval following extinction. Nature Communications, 2020, 11(1): 4358.
[17]
Klavir, O., Prigge, M., Sarel, A., Paz, R., Yizhar, O. Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex. Nature Neuroscience, 2017, 20(6): 836844.
[18]
Felix-Ortiz, A. C., Beyeler, A., Seo, C., Leppla, C. A., Wildes, C. P., Tye, K. M. BLA to vHPC inputs modulate anxiety-related behaviors. Neuron, 2013, 79(4): 658664.
[19]
Felix-Ortiz, A. C., Tye, K. M. Amygdala inputs to the ventral hippocampus bidirectionally modulate social behavior. The Journal of Neuroscience, 2014, 34(2): 586595.
[20]
Wang, Y., Liu, Z., Cai, L., Guo, R., Dong, Y., Huang, Y. H. A critical role of basolateral amygdala-to-nucleus accumbens projection in sleep regulation of reward seeking. Biological Psychiatry, 2020, 87(11): 954966.
[21]
Hsu, C. C., Madsen, T. E., O'Gorman, E., Gourley, S. L., Rainnie, D. G. Reward-related dynamical coupling between basolateral amygdala and nucleus accumbens. Brain Structure and Function, 2020, 225(6): 18731888.
[22]
Zhang, J. Y., Liu, T. H., He, Y., Pan, H. Q., Zhang, W. H., Yin, X. P., Tian, X. L., Li, B. M., Wang, X. D., Holmes, A. et al. Chronic stress remodels synapses in an amygdala circuit-specific manner. Biological Psychiatry, 2019, 85(3): 189201.
[23]
Sah, P., Faber, E. S., Lopez De Armentia, M., Power, J. The amygdaloid complex: Anatomy and physiology. Physiological Reviews, 2003, 83(3): 803834.
[24]
Smith, S. M., Vale, W. W. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues in Clinical Neuroscience, 2006, 8(4): 383395.
[25]
Anderson, R. M., Glanz, R. M., Johnson, S. B., Miller, M. M., Romig-Martin, S. A., Radley, J. J. Prolonged corticosterone exposure induces dendritic spine remodeling and attrition in the rat medial prefrontal cortex. Journal of Comparative Neurology, 2016, 524(18): 37293746.
[26]
Morales-Medina, J. C., Sanchez, F., Flores, G., Dumont, Y., Quirion, R. Morphological reorganization after repeated corticosterone administration in the hippocampus, nucleus accumbens and amygdala in the rat. Journal of Chemical Neuroanatomy, 2009, 38(4): 266272.
[27]
Gourley, S. L., Swanson, A. M., Koleske, A. J. Corticosteroid-induced neural remodeling predicts behavioral vulnerability and resilience. Journal of Neuroscience, 2013, 33(7): 31073112.
[28]
Zhang, W. H., Liu, W. Z., He, Y., You, W. J., Zhang, J. Y., Xu, H., Tian, X. L., Li, B. M., Mei, L., Holmes, A. et al. Chronic stress causes projection-specific adaptation of amygdala neurons via small-conductance calcium-activated potassium channel downregulation. Biological Psychiatry, 2019, 85(10): 812828.
[29]
McEwen, B. S. Glucocorticoids, depression, and mood disorders: Structural remodeling in the brain. Metabolism: Clinical and Experimental, 2005, 54(5 suppl 1): 2023.
[30]
LeDoux, J. The amygdala. Current Biololy, 2007, 17(20): R868R8674.
[31]
Pariante, C. M., Lightman, S. L. The HPA axis in major depression: Classical theories and new developments. Trends in Neurosciences, 2008, 31(9): 464468.
[32]
Meijer, O. C., Koorneef, L. L., Kroon, J. Glucocorticoid receptor modulators. Annales d’Endocrinologie, 2018, 79(3): 107111.
[33]
de Kloet, E. R., Sutanto, W., van den Berg, D. T. M., Carey, P., van Haarst, A. D., Hornsby, C. D., Meijer, O. C., Rots, N. Y., Oitzl, M. S. Brain mineralocorticoid receptor diversity: Functional implications.The Journal of Steoid Biochemistry and Molecular Biology, 1993, 47(1–6): 183190.
[34]
Evanson, N. K., Van Hooren, D. C., Herman, J. P. GluR5-mediated glutamate signaling regulates hypothalamo-pituitary-adrenocortical stress responses at the paraventricular nucleus and Median eminence. Aging Cell, 2009, 34(9): 13701379.
[35]
Cui, H., Sakamoto, H., Higashi, S., Kawata, M. Effects of single-prolonged stress on neurons and their afferent inputs in the amygdala. Neuroscience, 2008, 152(3): 703712.
[36]
Han, F., Ding, J., Shi, Y. Expression of amygdala mineralocorticoid receptor and glucocorticoid receptor in the single-prolonged stress rats. BMC Neuroscience, 2014, 15: 77.
[37]
Arnett, M. G., Pan, M. S., Doak, W., Cyr, P. E., Muglia, L. M., Muglia, L. J. The role of glucocorticoid receptor-dependent activity in the amygdala central nucleus and reversibility of early-life stress programmed behavior. Translational Psychiatry, 2015, 5: e542.
[38]
Cattaneo, A., Riva, M. A. Stress-induced mechanisms in mental illness: A role for glucocorticoid signalling. Journal of Environmental Management, 2016, 160: 169174.
[39]
Orock, A., Louwies, T., Yuan, T., Greenwood-Van Meerveld, B. Environmental enrichment prevents chronic stress-induced brain-gut axis dysfunction through a GR-mediated mechanism in the central nucleus of the amygdala. Neurogastroenterology and Motility, 2020, 32(6): e13826.
[40]
Barbayannis, G., Franco, D., Wong, S., Galdamez, J., Romeo, R. D., Bauer, E. P. Differential effects of stress on fear learning and activation of the amygdala in pre-adolescent and adult male rats. Neuroscience, 2017, 360: 210219.
[41]
Ganon-Elazar, E., Akirav, I. Cannabinoids and traumatic stress modulation of contextual fear extinction and GR expression in the amygdala-hippocampal-prefrontal circuit. Psychoneuroendocrinology, 2013, 38(9): 16751687.
[42]
Shilpa, B. M., Bhagya, V., Harish, G., Srinivas Bharath, M. M., Shankaranarayana Rao, B. S. Environmental enrichment ameliorates chronic immobilisation stress-induced spatial learning deficits and restores the expression of BDNF, VEGF, GFAP and glucocorticoid receptors. Progress in Neuro-psychopharmacology and Biological Psychiatry, 2017, 76: 88100.
[43]
Tripathi, S. J., Chakraborty, S., Srikumar, B. N., Raju, T. R., Shankaranarayana Rao, B. S. Prevention of chronic immobilization stress-induced enhanced expression of glucocorticoid receptors in the prefrontal cortex by inactivation of basolateral amygdala. Journal of Chemical Neuroanatomy, 2019, 95: 134145.
[44]
Wang, Q., Verweij, E. W. E., Krugers, H. J., Joels, M., Swaab, D. F., Lucassen, P. J. Distribution of the glucocorticoid receptor in the human amygdala; changes in mood disorder patients. Brain Structure and Function, 2014, 219(5): 16151626.
[45]
Miyata, S., Koyama, Y., Takemoto, K., Yoshikawa, K., Ishikawa, T., Taniguchi, M., Inoue, K., Aoki, M., Hori, O., Katayama, T. et al. Plasma corticosterone activates SGK1 and induces morphological changes in oligodendrocytes in corpus callosum. PLoS One, 2011, 6(5): e19859.
Stress and Brain
Pages 139-152
Cite this article:
Zhang Y-P, Zhong C-M, Wu L-X, et al. Glucocorticoid receptor, a potential mediator of differential regulation on amygdala neurons by chronic stress. Stress and Brain, 2022, 2(4): 139-152. https://doi.org/10.26599/SAB.2022.9060020

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Received: 17 July 2022
Revised: 19 September 2022
Accepted: 17 October 2022
Published: 30 November 2022
© The Author(s) 2022

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attributtion-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission.

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