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Review

From ligands to behavioral outcomes: understanding the role of mineralocorticoid receptors in brain function

ORCID Icon, ORCID Icon & ORCID Icon
Article: 2204366 | Received 22 Nov 2022, Accepted 13 Apr 2023, Published online: 08 May 2023

References

  • Anacker, C., Cattaneo, A., Luoni, A., Musaelyan, K., Zunszain, P. A., Milanesi, E., Rybka, J., Berry, A., Cirulli, F., Thuret, S., Price, J., Riva, M. A., Gennarelli, M., & Pariante, C. M. (2013). Glucocorticoid-related molecular signaling pathways regulating hippocampal neurogenesis. Neuropsychopharmacology: official Publication of the American College of Neuropsychopharmacology, 38(5), 1–17. https://doi.org/10.1038/npp.2012.253
  • Ancelin, M.-L., Scali, J., Norton, J., Ritchie, K., Dupuy, A.-M., Chaudieu, I., & Ryan, J. (2017). Heterogeneity in HPA axis dysregulation and serotonergic vulnerability to depression. Psychoneuroendocrinology, 77, 90–94. https://doi.org/10.1016/j.psyneuen.2016.11.016
  • Antoni, F. A. (2019). Magnocellular vasopressin and the mechanism of “glucocorticoid escape. Frontiers in Endocrinology, 10, 422. https://doi.org/10.3389/fendo.2019.00422
  • Arnal, J.-F., Lenfant, F., Metivier, R., Flouriot, G., Henrion, D., Adlanmerini, M., Fontaine, C., Gourdy, P., Chambon, P., Katzenellenbogen, B., & Katzenellenbogen, J. (2017). Membrane and nuclear estrogen receptor alpha actions: from tissue specificity to medical implications. Physiological Reviews, 97(3), 1045–1087. https://doi.org/10.1152/physrev.00024.2016
  • Arriza, J. L., Weinberger, C., Cerelli, G., Glaser, T. M., Handelin, B. L., Housman, D. E., & Evans, R. M. (1987). Cloning of human mineralocorticoid receptor complementary DNA: Structural and functional kinship with the glucocorticoid receptor. Science (New York, N.Y.), 237(4812), 268–275. https://doi.org/10.1126/science.3037703
  • Ashton, A. W., Le, T. Y. L., Gomez-Sanchez, C. E., Morel-Kopp, M.-C., McWhinney, B., Hudson, A., & Mihailidou, A. S. (2015). Role of nongenomic signaling pathways activated by aldosterone during cardiac reperfusion injury. Molecular Endocrinology (Baltimore, Md.), 29(8), 1144–1155. https://doi.org/10.1210/ME.2014-1410
  • Avital, A., Segal, M., & Richter-Levin, G. (2006). Contrasting roles of corticosteroid receptors in hippocampal plasticity. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 26(36), 9130–9134. https://doi.org/10.1523/JNEUROSCI.1628-06.2006
  • Baker, M. E., Funder, J. W., & Kattoula, S. R. (2013). Evolution of hormone selectivity in glucocorticoid and mineralocorticoid receptors. The Journal of Steroid Biochemistry and Molecular Biology, 137, 57–70. https://doi.org/10.1016/j.jsbmb.2013.07.009
  • Baker, M. E., & Katsu, Y. (2020). Progesterone: An enigmatic ligand for the mineralocorticoid receptor. Biochemical Pharmacology, 177, 113976. https://doi.org/10.1016/j.bcp.2020.113976
  • Bast, B.-O., Rickert, U., Schneppenheim, J., Cossais, F., Wilms, H., Arnold, P., & Lucius, R. (2018). Aldosterone exerts anti-inflammatory effects on LPS stimulated microglia. Heliyon, 4(10), e00826. https://doi.org/10.1016/j.heliyon.2018.e00826
  • Bay-Richter, C., Hallberg, L., Ventorp, F., Janelidze, S., & Brundin, L. (2012). Aldosterone synergizes with peripheral inflammation to induce brain IL-1β expression and depressive-like effects. Cytokine, 60(3), 749–754. https://doi.org/10.1016/j.cyto.2012.08.016
  • Belvederi Murri, M., Pariante, C., Mondelli, V., Masotti, M., Atti, A. R., Mellacqua, Z., Antonioli, M., Ghio, L., Menchetti, M., Zanetidou, S., Innamorati, M., & Amore, M. (2014). HPA axis and aging in depression: Systematic review and meta-analysis. Psychoneuroendocrinology, 41, 46–62. https://doi.org/10.1016/j.psyneuen.2013.12.004
  • Berardelli, R., Karamouzis, I., D’Angelo, V., Zichi, C., Fussotto, B., Giordano, R., Ghigo, E., & Arvat, E. (2013). Role of mineralocorticoid receptors on the hypothalamus–pituitary–adrenal axis in humans. Endocrine, 43(1), 51–58. https://doi.org/10.1007/s12020-012-9750-8
  • Berardelli, R., Karamouzis, I., Marinazzo, E., Prats, E., Picu, A., Giordano, R., Ghigo, E., & Arvat, E. (2010). Effect of acute and prolonged mineralocorticoid receptor blockade on spontaneous and stimulated hypothalamic–pituitary–adrenal axis in humans. European Journal of Endocrinology, 162(6), 1067–1074. https://doi.org/10.1530/EJE-09-1076
  • Berger, S., Wolfer, D. P., Selbach, O., Alter, H., Erdmann, G., Reichardt, H. M., Chepkova, A. N., Welzl, H., Haas, H. L., Lipp, H.-P., & Schütz, G. (2006). Loss of the limbic mineralocorticoid receptor impairs behavioral plasticity. Proceedings of the National Academy of Sciences of the United States of America, 103(1), 195–200. https://doi.org/10.1073/pnas.0503878102
  • Bisht, K., Sharma, K., & Tremblay, M.-È. (2018). Chronic stress as a risk factor for Alzheimer’s disease: Roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress. Neurobiology of Stress, 9, 9–21. https://doi.org/10.1016/j.ynstr.2018.05.003
  • Boero, G., Pisu, M. G., Biggio, F., Muredda, L., Carta, G., Banni, S., Paci, E., Follesa, P., Concas, A., Porcu, P., & Serra, M. (2018). Impaired glucocorticoid-mediated HPA axis negative feedback induced by juvenile social isolation in male rats. Neuropharmacology, 133, 242–253. https://doi.org/10.1016/j.neuropharm.2018.01.045
  • Bogdan, R., Perlis, R. H., Fagerness, J., & Pizzagalli, D. A. (2010). The impact of mineralocorticoid receptor ISO/VAL Genotype (rs5522) and stress on reward learning. Genes, Brain, and Behavior, 9(6), 658–667. https://doi.org/10.1111/j.1601-183X.2010.00600.x
  • Brinks, V., Berger, S., Gass, P., de Kloet, E. R., & Oitzl, M. S. (2009). Mineralocorticoid receptors in control of emotional arousal and fear memory. Hormones and Behavior, 56(2), 232–238. https://doi.org/10.1016/j.yhbeh.2009.05.003
  • Brocca, M. E., Pietranera, L., de Kloet, E. R., & De Nicola, A. F. (2019). Mineralocorticoid receptors, neuroinflammation and hypertensive encephalopathy. Cellular and Molecular Neurobiology, 39(4), 483–492. https://doi.org/10.1007/s10571-018-0610-9
  • Brown, N. J. (2008). Aldosterone and vascular inflammation. Hypertension (Dallas, Tex. : 1979), 51(2), 161–167. https://doi.org/10.1161/HYPERTENSIONAHA.107.095489
  • Buckley, T. M., Mullen, B. C., & Schatzberg, A. F. (2007). The acute effects of a mineralocorticoid receptor (MR) agonist on nocturnal hypothalamic–adrenal–pituitary (HPA) axis activity in healthy controls. Psychoneuroendocrinology, 32(8-10), 859–864. https://doi.org/10.1016/j.psyneuen.2007.05.016
  • Cameron, H. A., Woolley, C. S., McEwen, B. S., & Gould, E. (1993). Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience, 56(2), 337–344. https://doi.org/10.1016/0306-4522(93)90335-d
  • Chantong, B., Kratschmar, D. V., Nashev, L. G., Balazs, Z., & Odermatt, A. (2012). Mineralocorticoid and glucocorticoid receptors differentially regulate NF-kappaB activity and pro-inflammatory cytokine production in murine BV-2 microglial cells. Journal of Neuroinflammation, 9(1), 260. https://doi.org/10.1186/1742-2094-9-260
  • Chen, L., Shi, R., She, X., Gu, C., Chong, L., Zhang, L., & Li, R. (2020). Mineralocorticoid receptor antagonist-mediated cognitive improvement in a mouse model of Alzheimer’s type: Possible involvement of BDNF-H2 S-Nrf2 signaling. Fundamental & Clinical Pharmacology, 34(6), 697–707. https://doi.org/10.1111/fcp.12576
  • Chen, J., Wang, Z.-Z., Zhang, S., Chu, S.-F., Mou, Z., & Chen, N.-H. (2019). The effects of glucocorticoids on depressive and anxiety-like behaviors, mineralocorticoid receptor-dependent cell proliferation regulates anxiety-like behaviors. Behavioural Brain Research, 362, 288–298. https://doi.org/10.1016/j.bbr.2019.01.026
  • Chen, J., Wang, Z., Zhang, S., Zuo, W., & Chen, N. (2016). Does mineralocorticoid receptor play a vital role in the development of depressive disorder? Life Sciences, 152, 76–81. https://doi.org/10.1016/j.lfs.2016.03.022
  • Christy, C., Hadoke, P. W. F., Paterson, J. M., Mullins, J. J., Seckl, J. R., & Walker, B. R. (2003). 11beta-hydroxysteroid dehydrogenase type 2 in mouse aorta: Localization and influence on response to glucocorticoids. Hypertension (Dallas, Tex. : 1979), 42(4), 580–587. https://doi.org/10.1161/01.HYP.0000088855.06598.5B
  • Cizza, G., & Rother, K. I. (2012). Cortisol binding globulin: More than just a carrier? The Journal of Clinical Endocrinology and Metabolism, 97(1), 77–80. https://doi.org/10.1210/jc.2011-3090
  • Cole, T. J., & Young, M. J. (2017). 30 Years Of The Mineralocorticoid receptor: Mineralocorticoid receptor null mice: informing cell-type-specific roles. Journal of Endocrinology, 234(1), T83–T92. https://doi.org/10.1530/JOE-17-0155
  • Cornelisse, S., Joëls, M., & Smeets, T. (2011). A randomized trial on mineralocorticoid receptor blockade in men: Effects on stress responses, selective attention, and memory. Neuropsychopharmacology: official Publication of the American College of Neuropsychopharmacology, 36(13), 2720–2728. https://doi.org/10.1038/npp.2011.162
  • Couette, B., Fagart, J., Jalaguier, S., Lombes, M., Souque, A., & Rafestin-Oblin, M. E. (1996). Ligand-induced conformational change in the human mineralocorticoid receptor occurs within its hetero-oligomeric structure. Biochemical Journal, 315(2), 421–427. https://doi.org/10.1042/bj3150421
  • Coutinho, P., Vega, C., Pojoga, L. H., Rivera, A., Prado, G. N., Yao, T. M., Adler, G., Torres-Grajales, M., Maldonado, E. R., Ramos-Rivera, A., Williams, J. S., Williams, G., & Romero, J. R. (2014). Aldosterone’s rapid, nongenomic effects are mediated by striatin: A modulator of aldosterone’s effect on estrogen action. Endocrinology, 155(6), 2233–2243. https://doi.org/10.1210/en.2013-1834
  • de Abreu Feijó de Mello, A., Feijó de Mello, M., Carpenter, L. L., & Price, L. H. (2003). Update on stress and depression: The role of the hypothalamic-pituitary-adrenal (HPA) axis. Revista Brasileira de Psiquiatria (Sao Paulo, Brazil : 1999), 25(4), 231–238. https://doi.org/10.1590/s1516-44462003000400010
  • den Boon, F. S., & Sarabdjitsingh, R. A. (2017). Circadian and ultradian patterns of HPA-axis activity in rodents: Significance for brain functionality. Best Practice & Research: Clinical Endocrinology & Metabolism, 31(5), 445–457. https://doi.org/10.1016/j.beem.2017.09.001
  • de Kloet, E. R., Fitzsimons, C. P., Datson, N. A., Meijer, O. C., & Vreugdenhil, E. (2009). Glucocorticoid signaling and stress-related limbic susceptibility pathway: About receptors, transcription machinery and microRNA. Brain Research, 1293, 129–141. https://doi.org/10.1016/j.brainres.2009.03.039
  • De Nicola, A. F., Meyer, M., Guennoun, R., Schumacher, M., Hunt, H., Belanoff, J., de Kloet, E. R., & Gonzalez Deniselle, M. C. (2020). Insights into the therapeutic potential of glucocorticoid receptor modulators for neurodegenerative diseases. International Journal of Molecular Sciences, 21(6), 2137. https://doi.org/10.3390/ijms21062137
  • De Nobrega, A. K., Luz, K. V., & Lyons, L. C. (2020). Resetting the aging clock: Implications for managing age-related diseases. In P. C. Guest (Ed.), Reviews on new drug targets in age-related disorders (pp. 193–265). Springer International Publishing. https://doi.org/10.1016/j.beem.2017.09.001
  • DeRijk, R. H., van Leeuwen, N., Klok, M. D., & Zitman, F. G. (2008). Corticosteroid receptor-gene variants: Modulators of the stress-response and implications for mental health. European Journal of Pharmacology, 585(2-3), 492–501. https://doi.org/10.1016/j.ejphar.2008.03.012
  • Deuter, C. E., Wingenfeld, K., Schultebraucks, K., Hellmann-Regen, J., Piber, D., & Otte, C. (2017). Effects of mineralocorticoid-receptor stimulation on risk taking behavior in young healthy men and women. Psychoneuroendocrinology, 75, 132–140. https://doi.org/10.1016/j.psyneuen.2016.10.018
  • Doetsch, F., Caillé, I., Lim, D. A., García-Verdugo, J. M., & Alvarez-Buylla, A. (1999). Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell, 97(6), 703–716. https://doi.org/10.1016/s0092-8674(00)80783-7
  • Edwards, C. R., Stewart, P. M., Burt, D., Brett, L., McIntyre, M. A., Sutanto, W. S., de Kloet, E. R., & Monder, C. (1988). Localisation of 11 beta-hydroxysteroid dehydrogenase—Tissue specific protector of the mineralocorticoid receptor. Lancet (London, England), 2(8618), 986–989. https://doi.org/10.1016/s0140-6736(88)90742-8
  • Endedijk, H. M., Nelemans, S. A., Schür, R. R., Boks, M. P. M., van Lier, P., Meeus, W., Branje, S., & Vinkers, C. H. (2020). The role of stress and mineralocorticoid receptor haplotypes in the development of symptoms of depression and anxiety during adolescence. Frontiers in Psychiatry, 11, 367. https://doi.org/10.3389/fpsyt.2020.00367
  • Fan, Y. S., Eddy, R. L., Byers, M. G., Haley, L. L., Henry, W. M., Nowak, N. J., & Shows, T. B. (1989). The human mineralocorticoid receptor gene (MLR) is located on chromosome 4 at q31.2. Cytogenetics and Cell Genetics, 52(1-2), 83–84. https://doi.org/10.1159/000132846
  • Faresse, N. (2014). Post-translational modifications of the mineralocorticoid receptor: How to dress the receptor according to the circumstances? The Journal of Steroid Biochemistry and Molecular Biology, 143, 334–342. https://doi.org/10.1016/j.jsbmb.2014.04.015
  • Faye, C., McGowan, J. C., Denny, C. A., & David, D. J. (2018). Neurobiological mechanisms of stress resilience and implications for the aged population. Current Neuropharmacology, 16(3), 234–270. https://doi.org/10.2174/1570159X15666170818095105
  • Fink, G. (2016). Stress: Neuroendocrinology and Neurobiology: Handbook of Stress Series. Academic Press.
  • Finsterwald, C., & Alberini, C. M. (2014). Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: From adaptive responses to psychopathologies. Neurobiology of Learning and Memory, 112, 17–29. https://doi.org/10.1016/j.nlm.2013.09.017
  • Fischer, K., Kelly, S. M., Watt, K., Price, N. C., & McEwan, I. J. (2010). Conformation of the mineralocorticoid receptor n-terminal domain: Evidence for induced and stable structure. Molecular Endocrinology (Baltimore, Md.), 24(10), 1935–1948. https://doi.org/10.1210/me.2010-0005
  • Fischer, A. K., von Rosenstiel, P., Fuchs, E., Goula, D., Almeida, O. F. X., & Czéh, B. (2002). The prototypic mineralocorticoid receptor agonist aldosterone influences neurogenesis in the dentate gyrus of the adrenalectomized rat. Brain Research, 947(2), 290–293. https://doi.org/10.1016/s0006-8993(02)03042-1
  • Fox, A. S., Oler, J. A., Birn, R. M., Shackman, A. J., Alexander, A. L., & Kalin, N. H. (2018). Functional connectivity within the primate extended amygdala is heritable and associated with early-life anxious temperament. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 38(35), 7611–7621. https://doi.org/10.1523/JNEUROSCI.0102-18.2018
  • Fru, K. N., VandeVoort, C. A., & Chaffin, C. L. (2006). Mineralocorticoid synthesis during the periovulatory interval in macaques. Biology of Reproduction, 75(4), 568–574. https://doi.org/10.1095/biolreprod.106.053470
  • Fujioka, A., Fujioka, T., Ishida, Y., Maekawa, T., & Nakamura, S. (2006). Differential effects of prenatal stress on the morphological maturation of hippocampal neurons. Neuroscience, 141(2), 907–915. https://doi.org/10.1016/j.neuroscience.2006.04.046
  • Fujioka, T., Fujioka, A., Tan, N., Chowdhury, G. M., Mouri, H., Sakata, Y., & Nakamura, S. (2001). Mild prenatal stress enhances learning performance in the non-adopted rat offspring. Neuroscience, 103(2), 301–307. https://doi.org/10.1016/s0306-4522(00)00582-0
  • Fujioka, T., Sakata, Y., Yamaguchi, K., Shibasaki, T., Kato, H., & Nakamura, S. (1999). The effects of prenatal stress on the development of hypothalamic paraventricular neurons in fetal rats. Neuroscience, 92(3), 1079–1088. https://doi.org/10.1016/s0306-4522(99)00073-1
  • Fuller, P. J. (2015). Novel interactions of the mineralocorticoid receptor. Molecular and Cellular Endocrinology, 408, 33–37. https://doi.org/10.1016/j.mce.2015.01.027
  • Fuller, P. J., & Verity, K. (1990). Mineralocorticoid receptor gene expression in the gastrointestinal tract: Distribution and ontogeny. Journal of Steroid Biochemistry, 36(4), 263–267. https://doi.org/10.1016/0022-4731(90)90215-e
  • Fuller, P. J., Yao, Y., Yang, J., & Young, M. J. (2012). Mechanisms of ligand specificity of the mineralocorticoid receptor. The Journal of Endocrinology, 213(1), 15–24. https://doi.org/10.1530/JOE-11-0372
  • Fuller, P. J., & Young, M. J. (2005). Mechanisms of mineralocorticoid action. Hypertension (Dallas, Tex. : 1979), 46(6), 1227–1235. https://doi.org/10.1161/01.HYP.0000193502.77417.17
  • Funder, J. W. (1991). Steroids, receptors, and response elements: The limits of signal specificity. Recent Progress in Hormone Research, 47, 191–207. discussion 207-210. https://doi.org/10.1016/b978-0-12-571147-0.50010-x
  • Funder, J. W., Pearce, P. T., Smith, R., & Smith, A. I. (1988). Mineralocorticoid action: Target tissue specificity is enzyme, not receptor, mediated. Science (New York, N.Y.), 242(4878), 583–585. https://doi.org/10.1126/science.2845584
  • Gadasheva, Y., Nolze, A., & Grossmann, C. (2021). Posttranslational modifications of the mineralocorticoid receptor and cardiovascular aging. Frontiers in Molecular Biosciences, 8, 667990. https://doi.org/10.3389/fmolb.2021.667990
  • Gaffey, A. E., Bergeman, C. S., Clark, L. A., & Wirth, M. M. (2016). Aging and the HPA axis: Stress and resilience in older adults. Neuroscience and Biobehavioral Reviews, 68, 928–945. https://doi.org/10.1016/j.neubiorev.2016.05.036
  • Gasparini, S., Resch, J. M., Narayan, S. V., Peltekian, L., Iverson, G. N., Karthik, S., & Geerling, J. C. (2019). Aldosterone-sensitive HSD2 neurons in mice. Brain Structure & Function, 224(1), 387–417. https://doi.org/10.1007/s00429-018-1778-y
  • Gass, P., Kretz, O., Wolfer, D. P., Berger, S., Tronche, F., Reichardt, H. M., Kellendonk, C., Lipp, H.-P., Schmid, W., & Schütz, G. (2000). Genetic disruption of mineralocorticoid receptor leads to impaired neurogenesis and granule cell degeneration in the hippocampus of adult mice. EMBO Reports, 1(5), 447–451. https://doi.org/10.1093/embo-reports/kvd088
  • GBD 2019 Mental Disorders Collaborators. (2022). Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. The Lancet. Psychiatry, 9(2), 137–150. https://doi.org/10.1016/S2215-0366(21)00395-3
  • Geerling, J. C., Kawata, M., & Loewy, A. D. (2006). Aldosterone-sensitive neurons in the rat central nervous system. The Journal of Comparative Neurology, 494(3), 515–527. https://doi.org/10.1002/cne.20808
  • Gesing, A., Bilang-Bleuel, A., Droste, S. K., Linthorst, A. C., Holsboer, F., & Reul, J. M. (2001). Psychological stress increases hippocampal mineralocorticoid receptor levels: Involvement of corticotropin-releasing hormone. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 21(13), 4822–4829. https://doi.org/10.1523/JNEUROSCI.21-13-04822.2001
  • Gomez-Sanchez, E. (2014). Brain mineralocorticoid receptors in cognition and cardiovascular homeostasis. Steroids, 91, 20–31. https://doi.org/10.1016/j.steroids.2014.08.014
  • Gomez-Sanchez, E., & Gomez-Sanchez, C. E. (2014). The multifaceted mineralocorticoid receptor. In R. Terjung (Ed.), Comprehensive Physiology (1st ed., pp. 965–994). Wiley. https://doi.org/10.1002/cphy
  • Goncharova, N. D. (2020). The HPA axis under stress and aging: individual vulnerability is associated with behavioral patterns and exposure time. BioEssays, 42(9), 2000007. https://doi.org/10.1002/bies.202000007
  • Goncharova, N. D., & Oganyan, T. E. (2018). Age-related differences in stress responsiveness of the hypothalamic-pituitary-adrenal axis of nonhuman primates with various types of adaptive behavior. General and Comparative Endocrinology, 258, 163–172. https://doi.org/10.1016/j.ygcen.2017.08.007
  • Gorini, S., Kim, S. K., Infante, M., Mammi, C., La Vignera, S., Fabbri, A., Jaffe, I. Z., & Caprio, M. (2019). Role of Aldosterone and Mineralocorticoid Receptor in Cardiovascular Aging. Frontiers in Endocrinology, 10, 584. https://doi.org/10.3389/fendo.2019.00584
  • Groeneweg, F. L., Karst, H., de Kloet, E. R., & Joëls, M. (2012). Mineralocorticoid and glucocorticoid receptors at the neuronal membrane, regulators of nongenomic corticosteroid signalling. Molecular and Cellular Endocrinology, 350(2), 299–309. https://doi.org/10.1016/j.mce.2011.06.020
  • Grossmann, C., Almeida-Prieto, B., Nolze, A., & Alvarez de la Rosa, D. (2022). Structural and molecular determinants of mineralocorticoid receptor signalling. British Journal of Pharmacology, 179(13), 3103–3118. https://doi.org/10.1111/bph.15746
  • Grottoli, S., Giordano, R., Maccagno, B., Pellegrino, M., Ghigo, E., & Arvat, E. (2002). The stimulatory effect of canrenoate, a mineralocorticoid antagonist, on the activity of the hypothalamus-pituitary-adrenal axis is abolished by alprazolam, a benzodiazepine, in humans. The Journal of Clinical Endocrinology and Metabolism, 87(10), 4616–4620. https://doi.org/10.1210/jc.2002-020331
  • Gulyaeva, N. V. (2021). Glucocorticoid Regulation of the GlutamatergicSynapse: Mechanisms of Stress-Dependent Neuroplasticity. Journal of Evolutionary Biochemistry and Physiology, 57(3), 564–576. https://doi.org/10.1134/S0022093021030091
  • Gupta, A. (2019). Role of stress and hormones of the Hypothalamic-Pituitary-Adrenal (HPA) axis in aging. In P. C. Rath (Ed.), Models, molecules and mechanisms in biogerontology: physiological abnormalities, diseases and interventions (pp. 241–263). Springer. https://doi.org/10.1007/978-981-13-3585-3
  • Haleem, D. J., & Gul, S. (2020). Circulating leptin, cortisol and gender differences associated with anorexia or obesity in depression. The World Journal of Biological Psychiatry: The Official Journal of the World Federation of Societies of Biological Psychiatry, 21(3), 195–202. https://doi.org/10.1080/15622975.2019.1648870
  • Hassan, A. H., von Rosenstiel, P., Patchev, V. K., Holsboer, F., & Almeida, O. F. (1996). Exacerbation of apoptosis in the dentate gyrus of the aged rat by dexamethasone and the protective role of corticosterone. Experimental Neurology, 140(1), 43–52. https://doi.org/10.1006/exnr.1996.0113
  • Hayashi, G., & Cortopassi, G. (2015). Oxidative stress in inherited mitochondrial diseases. Free Radical Biology & Medicine, 88(Pt A), 10–17. https://doi.org/10.1016/j.freeradbiomed.2015.05.039
  • Heim, C., Newport, D. J., Heit, S., Graham, Y. P., Wilcox, M., Bonsall, R., Miller, A. H., & Nemeroff, C. B. (2000). Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA, 284(5), 592–597. https://doi.org/10.1001/jama.284.5.592
  • Herman, J. P., McKlveen, J. M., Ghosal, S., Kopp, B., Wulsin, A., Makinson, R., Scheimann, J., & Myers, B. (2016). Regulation of the hypothalamic-pituitary-adrenocortical stress response. Comprehensive Physiology, 6(2), 603–621. https://doi.org/10.1016/0006-8993(95)00152-g
  • Herman, J. P., & Watson, S. J. (1995). Stress regulation of mineralocorticoid receptor heteronuclear RNA in rat hippocampus. Brain Research, 677(2), 243–249. https://doi.org/10.1016/0006-8993(95)00152-g
  • Hermidorff, M. M., de Assis, L. V. M., & Isoldi, M. C. (2017). Genomic and rapid effects of aldosterone: What we know and do not know thus far. Heart Failure Reviews, 22(1), 65–89. https://doi.org/10.1007/s10741-016-9591-2
  • Hlavacova, N., & Jezova, D. (2008). Chronic treatment with the mineralocorticoid hormone aldosterone results in increased anxiety-like behavior. Hormones and Behavior, 54(1), 90–97. https://doi.org/10.1016/j.yhbeh.2008.02.004
  • Hlavacova, N., Wes, P. D., Ondrejcakova, M., Flynn, M. E., Poundstone, P. K., Babic, S., Murck, H., & Jezova, D. (2012). Subchronic treatment with aldosterone induces depression-like behaviours and gene expression changes relevant to major depressive disorder. The International Journal of Neuropsychopharmacology, 15(2), 247–265. https://doi.org/10.1017/S1461145711000368
  • Hood, S., & Amir, S. (2017). The aging clock: Circadian rhythms and later life. The Journal of Clinical Investigation, 127(2), 437–446. https://doi.org/10.1172/JCI90328
  • Hudson, W. H., Youn, C., & Ortlund, E. A. (2014). Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA. PloS One, 9(9), e107000. https://doi.org/10.1371/journal.pone.0107000
  • Izakova, L., Hlavacova, N., Segeda, V., Kapsdorfer, D., Morovicsova, E., & Jezova, D. (2020). Salivary aldosterone, cortisol, and their morning to evening slopes in patients with depressive disorder and healthy subjects: acute episode and follow-up 6 months after reaching remission. Neuroendocrinology, 110(11-12), 1001–1009. https://doi.org/10.1159/000505921
  • Joëls, M. (2001). Corticosteroid actions in the hippocampus: Corticosteroid actions in the hippocampus. Journal of Neuroendocrinology, 13(8), 657–669. https://doi.org/10.1046/j.1365-2826.2001.00688.x
  • Joëls, M. (2008). Functional actions of corticosteroids in the hippocampus. European Journal of Pharmacology, 583(2-3), 312–321. https://doi.org/10.1016/j.ejphar.2007.11.064
  • Joëls, M., Sarabdjitsingh, R. A., & Karst, H. (2012). Unraveling the time domains of corticosteroid hormone influences on brain activity: Rapid, slow, and chronic modes. Pharmacological Reviews, 64(4), 901–938. https://doi.org/10.1124/pr.112.005892
  • Jurkowski, M. P., Bettio, L., K Woo, E., Patten, A., Yau, S.-Y., & Gil-Mohapel, J. (2020). Beyond the hippocampus and the SVZ: adult neurogenesis throughout the brain. Frontiers in Cellular Neuroscience, 14, 576444. https://doi.org/10.3389/fncel.2020.576444
  • Juruena, M. F., Bocharova, M., Agustini, B., & Young, A. H. (2018). Atypical depression and non-atypical depression: Is HPA axis function a biomarker? A systematic review. Journal of Affective Disorders, 233, 45–67. https://doi.org/10.1016/j.jad.2017.09.052
  • Juruena, M. F., Gama, C. S., Berk, M., & Belmonte-de-Abreu, P. S. (2009). Improved stress response in bipolar affective disorder with adjunctive spironolactone (mineralocorticoid receptor antagonist): Case series. Journal of Psychopharmacology (Oxford, England), 23(8), 985–987. https://doi.org/10.1177/0269881108092121
  • Karandrea, D., Kittas, C., & Kitraki, E. (2000). Contribution of sex and cellular context in the regulation of brain corticosteroid receptors following restraint stress. Neuroendocrinology, 71(6), 343–353. https://doi.org/10.1159/000054555
  • Karst, H., Berger, S., Turiault, M., Tronche, F., Schütz, G., & Joëls, M. (2005). Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone. Proceedings of the National Academy of Sciences of the United States of America, 102(52), 19204–19207. https://doi.org/10.1073/pnas.0507572102
  • Karst, H., den Boon, F. S., Vervoort, N., Adrian, M., Kapitein, L. C., & Joëls, M. (2022). Non-genomic steroid signaling through the mineralocorticoid receptor: Involvement of a membrane-associated receptor? Molecular and Cellular Endocrinology, 541, 111501. https://doi.org/10.1016/j.mce.2021.111501
  • Keller, J., Gomez, R., Williams, G., Lembke, A., Lazzeroni, L., Murphy, G. M., & Schatzberg, A. F. (2017). HPA axis in major depression: cortisol, clinical symptomatology, and genetic variation predict cognition. Molecular Psychiatry, 22(4), 527–536. https://doi.org/10.1038/mp.2016.120
  • Keller-Wood, M. E., & Dallman, M. F. (1984). Corticosteroid inhibition of ACTH secretion. Endocrine Reviews, 5(1), 1–24. https://doi.org/10.1210/edrv-5-1-1
  • Kellner, M., Baker, D. G., Yassouridis, A., Bettinger, S., Otte, C., Naber, D., & Wiedemann, K. (2002). Mineralocorticoid receptor function in patients with posttraumatic stress disorder. The American Journal of Psychiatry, 159(11), 1938–1940. https://doi.org/10.1176/appi.ajp.159.11.1938
  • Kellner, M., Otte, C., Yassouridis, A., Schick, M., Jahn, H., & Wiedemann, K. (2004). Overnight metyrapone and combined dexamethasone/metyrapone tests in post-traumatic stress disorder: Preliminary findings. European Neuropsychopharmacology : The Journal of the European College of Neuropsychopharmacology, 14(4), 337–339. https://doi.org/10.1016/j.euroneuro.2003.11.002
  • Kellner, M., & Wiedemann, K. (2008). Mineralocorticoid receptors in brain, in health and disease: Possibilities for new pharmacotherapy. European Journal of Pharmacology, 583(2-3), 372–378. https://doi.org/10.1016/j.ejphar.2007.07.072
  • Kempermann, G., Song, H., & Gage, F. H. (2015). Neurogenesis in the Adult Hippocampus. Cold Spring Harbor Perspectives in Biology, 7(9), a018812. https://doi.org/10.1101/cshperspect.a018812
  • Kennedy, C. L. M., Carter, S. D., Mifsud, K. R., & Reul, J. M. H. M. (2020). Unexpected effects of metyrapone on corticosteroid receptor interaction with the genome and subsequent gene transcription in the hippocampus of male rats. Journal of Neuroendocrinology, 32(2), e12820. https://doi.org/10.1111/jne.12820
  • Kitraki, E., Kremmyda, O., Youlatos, D., Alexis, M. N., & Kittas, C. (2004). Gender-dependent alterations in corticosteroid receptor status and spatial performance following 21 days of restraint stress. Neuroscience, 125(1), 47–55. https://doi.org/10.1016/j.neuroscience.2003.12.024
  • Kline, S. A., & Mega, M. S. (2020). Stress-Induced neurodegeneration: the potential for coping as neuroprotective therapy. American Journal of Alzheimer’s Disease and Other Dementias, 35, 1533317520960873. https://doi.org/10.1177/1533317520960873
  • Kloet, E. R. D., Vreugdenhil, E., Oitzl, M. S., & Ls, M. J. (1998). Brain corticosteroid receptor balance in health and disease. Brain Corticosteroid Receptors, 19(3), 33.
  • Klok, M. D., Alt, S. R., Irurzun Lafitte, A. J. M., Turner, J. D., Lakke, E. A. J. F., Huitinga, I., Muller, C. P., Zitman, F. G., Ronald de Kloet, E., & DeRijk, R. H. (2011a). Decreased expression of mineralocorticoid receptor mRNA and its splice variants in postmortem brain regions of patients with major depressive disorder. Journal of Psychiatric Research, 45(7), 871–878. https://doi.org/10.1016/j.jpsychires.2010.12.002
  • Klok, M. D., Giltay, E. J., Van der Does, A. J. W., Geleijnse, J. M., Antypa, N., Penninx, B. W. J. H., de Geus, E. J. C., Willemsen, G., Boomsma, D. I., van Leeuwen, N., Zitman, F. G., de Kloet, E. R., & DeRijk, R. H. (2011b). A common and functional mineralocorticoid receptor haplotype enhances optimism and protects against depression in females. Translational Psychiatry, 1(12), e62. https://doi.org/10.1038/tp.2011.59
  • Knutti, D., Kaul, A., & Kralli, A. (2000). A tissue-specific coactivator of steroid receptors, identified in a functional genetic screen. Molecular and Cellular Biology, 20(7), 2411–2422. https://doi.org/10.1128/MCB.20.7.2411-2422.2000
  • Koning, A.-S C. A. M., Buurstede, J. C., van Weert, L. T. C. M., & Meijer, O. C. (2019). Glucocorticoid and mineralocorticoid receptors in the brain: a transcriptional perspective. Journal of the Endocrine Society, 3(10), 1917–1930. https://doi.org/10.1210/js.2019-00158
  • Kuningas, M., de Rijk, R. H., Westendorp, R. G. J., Jolles, J., Slagboom, P. E., & van Heemst, D. (2007). Mental performance in old age dependent on cortisol and genetic variance in the mineralocorticoid and glucocorticoid receptors. Neuropsychopharmacology : official Publication of the American College of Neuropsychopharmacology, 32(6), 1295–1301. https://doi.org/10.1038/sj.npp.1301260
  • Kwak, S. P., Patel, P. D., Thompson, R. C., Akil, H., & Watson, S. J. (1993). 5’-Heterogeneity of the mineralocorticoid receptor messenger ribonucleic acid: Differential expression and regulation of splice variants within the rat hippocampus. Endocrinology, 133(5), 2344–2350. https://doi.org/10.1210/endo.133.5.8404687
  • Lai, M., Horsburgh, K., Bae, S.-E., Carter, R. N., Stenvers, D. J., Fowler, J. H., Yau, J. L., Gomez-Sanchez, C. E., Holmes, M. C., Kenyon, C. J., Seckl, J. R., & Macleod, M. R. (2007). Forebrain mineralocorticoid receptor overexpression enhances memory, reduces anxiety and attenuates neuronal loss in cerebral ischaemia: Increased mineralocorticoid receptor is protective. The European Journal of Neuroscience, 25(6), 1832–1842. https://doi.org/10.1111/j.1460-9568.2007.05427.x
  • Lainscak, M., Pelliccia, F., Rosano, G., Vitale, C., Schiariti, M., Greco, C., Speziale, G., & Gaudio, C. (2015). Safety profile of mineralocorticoid receptor antagonists: Spironolactone and eplerenone. International Journal of Cardiology, 200, 25–29. https://doi.org/10.1016/j.ijcard.2015.05.127
  • Le Moëllic, C., Ouvrard-Pascaud, A., Capurro, C., Cluzeaud, F., Fay, M., Jaisser, F., Farman, N., & Blot-Chabaud, M. (2004). Early nongenomic events in aldosterone action in renal collecting duct cells: PKCalpha activation, mineralocorticoid receptor phosphorylation, and cross-talk with the genomic response. Journal of the American Society of Nephrology: JASN, 15(5), 1145–1160.
  • Liu, Z., Wong, J., Tsai, S. Y., Tsai, M. J., & O’Malley, B. W. (1999). Steroid receptor coactivator-1 (SRC-1) enhances ligand-dependent and receptor-dependent cell-free transcription of chromatin. Proceedings of the National Academy of Sciences of the United States of America, 96(17), 9485–9490. https://doi.org/10.1073/pnas.96.17.9485
  • Lombès, M., Binart, N., Delahaye, F., Baulieu, E. E., & Rafestin-Oblin, M. E. (1994). Differential intracellular localization of human mineralocorticosteroid receptor on binding of agonists and antagonists. Biochemical Journal, 302(1), 191–197. https://doi.org/10.1042/bj3020191
  • Lupien, S. J., Juster, R.-P., Raymond, C., & Marin, M.-F. (2018). The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity. Frontiers in Neuroendocrinology, 49, 91–105. https://doi.org/10.1016/j.yfrne.2018.02.001
  • Lupien, S. J., & McEwen, B. S. (1997). The acute effects of corticosteroids on cognition: Integration of animal and human model studies. Brain Research. Brain Research Reviews, 24(1), 1–27. https://doi.org/10.1016/s0165-0173(97)00004-0
  • Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schütz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., & Evans, R. M. (1995). The Nuclear Receptor Superfamily: The Second Decade. Cell, 83(6), 835–839. https://doi.org/10.1016/0092-8674(95)90199-x
  • Marver, D., Stewart, J., Funder, J. W., Feldman, D., & Edelman, I. S. (1974). Renal Aldosterone Receptors: Studies with [3H]Aldosterone and the Anti-Mineralocorticoid [3H]Spirolactone (SC-26304). Proceedings of the National Academy of Sciences of the United States of America, 71(4), 1431–1435. https://doi.org/10.1073/pnas.71.4.1431
  • Marzolla, V., Armani, A., Feraco, A., De Martino, M. U., Fabbri, A., Rosano, G., & Caprio, M. (2014). Mineralocorticoid receptor in adipocytes and macrophages: A promising target to fight metabolic syndrome. Steroids, 91, 46–53. https://doi.org/10.1016/j.steroids.2014.05.001
  • McEown, K., & Treit, D. (2011). Mineralocorticoid receptors in the medial prefrontal cortex and hippocampus mediate rats’ unconditioned fear behaviour. Hormones and Behavior, 60(5), 581–588. https://doi.org/10.1016/j.yhbeh.2011.08.007
  • McKenna, N. J., Lanz, R. B., & O’Malley, B. W. (1999). Nuclear receptor coregulators: Cellular and molecular biology. Endocrine Reviews, 20(3), 321–344. https://doi.org/10.1210/edrv.20.3.0366
  • Medina, A., Seasholtz, A. F., Sharma, V., Burke, S., Bunney, W., Myers, R. M., Schatzberg, A., Akil, H., & Watson, S. J. (2013). Glucocorticoid and Mineralocorticoid Receptor Expression in the Human Hippocampus in Major Depressive Disorder. Journal of Psychiatric Research, 47(3), 307–314. https://doi.org/10.1016/j.jpsychires.2012.11.002
  • Meijer, O. C., Koorneef, L. L., & Kroon, J. (2018). Glucocorticoid receptor modulators. Annales D’endocrinologie, 79(3), 107–111. https://doi.org/10.1016/j.ando.2018.03.004
  • Meijer, O. C., Steenbergen, P. J., & de Kloet, E. R. (2000). Differential expression and regional distribution of steroid receptor coactivators SRC-1 and SRC-2 in brain and pituitary*. Endocrinology, 141(6), 2192–2199. https://doi.org/10.1210/endo.141.6.7489
  • Meltzer, H. (1989). Serotonergic dysfunction in depression. British Journal of Psychiatry, 155(S8), 25–31. https://doi.org/10.1192/S0007125000291733
  • Meltzer, H. Y. (1990). Role of serotonin in depressiona. Annals of the New York Academy of Sciences, 600(1), 486–499. https://doi.org/10.1111/j.1749-6632.1990.tb16904.x
  • Mifsud, K. R., & Reul, J. M. H. M. (2018). Mineralocorticoid and glucocorticoid receptor-mediated control of genomic responses to stress in the brain. Stress (Amsterdam, Netherlands), 21(5), 389–402. https://doi.org/10.1080/10253890.2018.1456526
  • Miller, M. W., & Sadeh, N. (2014). Traumatic stress, oxidative stress and post-traumatic stress disorder: Neurodegeneration and the accelerated-aging hypothesis. Molecular Psychiatry, 19(11), 1156–1162. https://doi.org/10.1038/mp.2014.111
  • Mitra, R., Ferguson, D., & Sapolsky, R. M. (2009). Mineralocorticoid receptor overexpression in basolateral amygdala reduces corticosterone secretion and anxiety. Biological Psychiatry, 66(7), 686–690. https://doi.org/10.1016/j.biopsych.2009.04.016
  • Montaron, M. F., Piazza, P. V., Aurousseau, C., Urani, A., Le Moal, M., & Abrous, D. N. (2003). Implication of corticosteroid receptors in the regulation of hippocampal structural plasticity. The European Journal of Neuroscience, 18(11), 3105–3111. https://doi.org/10.1111/j.1460-9568.2003.03048.x
  • Morrison, N., Harrap, S., Arriza, J., Boyd, E., & Connor, J. M. (1990). Regional chromosomal assignment of the human mineralocorticoid receptor gene to 4q31.1. Human Genetics, 85(1), 130–132. https://doi.org/10.1007/BF00276340
  • Motivala, A., & Pitt, B. (2007). Drospirenone for oral contraception and hormone replacement therapy: Are its cardiovascular risks and benefits the same as other progestogens? Drugs, 67(5), 647–655. https://doi.org/10.2165/00003495-200767050-00001
  • Muhtz, C., Zyriax, B.-C., Bondy, B., Windler, E., & Otte, C. (2011). Association of a common mineralocorticoid receptor gene polymorphism with salivary cortisol in healthy adults. Psychoneuroendocrinology, 36(2), 298–301. https://doi.org/10.1016/j.psyneuen.2010.08.003
  • Murck, H., Adolf, C., Schneider, A., Schlageter, L., Heinrich, D., Ritzel, K., Sturm, L., Quinkler, M., Beuschlein, F., Reincke, M., & Künzel, H. (2021). Differential effects of reduced mineralocorticoid receptor activation by unilateral adrenalectomy vs mineralocorticoid antagonist treatment in patients with primary aldosteronism—Implications for depression and anxiety. Journal of Psychiatric Research, 137, 376–382. https://doi.org/10.1016/j.jpsychires.2021.02.064
  • Murck, H., Büttner, M., Kircher, T., & Konrad, C. (2014). Genetic, molecular and clinical determinants for the involvement of aldosterone and its receptors in major depression. Nephron. Physiology, 128(1-2), 17–25. https://doi.org/10.1159/000368265
  • Myers, B., McKlveen, J. M., & Herman, J. P. (2014). Glucocorticoid actions on synapses, circuits, and behavior: Implications for the energetics of stress. Frontiers in Neuroendocrinology, 35(2), 180–196. https://doi.org/10.1016/j.yfrne.2013.12.003
  • Nagata, Y., Goto, T., & Miyamoto, H. (2019). The role of mineralocorticoid receptor signaling in genitourinary cancers. Nuclear Receptor Research, 6, https://doi.org/10.32527/2019/101410
  • Nakamura, T., Girerd, S., Jaisser, F., & Barrera-Chimal, J. (2022). Nonepithelial mineralocorticoid receptor activation as a determinant of kidney disease. Kidney International Supplements, 12(1), 12–18. https://doi.org/10.1016/j.kisu.2021.11.004
  • Neylan, T. C., Lenoci, M., Maglione, M. L., Rosenlicht, N. Z., Metzler, T. J., Otte, C., Schoenfeld, F. B., Yehuda, R., & Marmar, C. R. (2003). Delta sleep response to metyrapone in post-traumatic stress disorder. Neuropsychopharmacology: official Publication of the American College of Neuropsychopharmacology, 28(9), 1666–1676. https://doi.org/10.1038/sj.npp.1300215
  • Nicolaides, N. C., Kino, T., Roberts, M. L., Katsantoni, E., Sertedaki, A., Moutsatsou, P., Psarra, A.-M G., Chrousos, G. P., & Charmandari, E. (2017). The role of S-palmitoylation of the Human Glucocorticoid Receptor (hGR) in mediating the nongenomic glucocorticoid actions. Journal of Molecular Biochemistry, 6(1), 3–12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538142/
  • Odermatt, A., & Atanasov, A. G. (2009). Mineralocorticoid receptors: Emerging complexity and functional diversity. Steroids, 74(2), 163–171. https://doi.org/10.1016/j.steroids.2008.10.010
  • Odermatt, A., & Kratschmar, D. V. (2012). Tissue-specific modulation of mineralocorticoid receptor function by 11β-hydroxysteroid dehydrogenases: An overview. Molecular and Cellular Endocrinology, 350(2), 168–186. https://doi.org/10.1016/j.mce.2011.07.020
  • Oh, H.-J., Song, M., Kim, Y. K., Bae, J. R., Cha, S.-Y., Bae, J. Y., Kim, Y., You, M., Lee, Y., Shim, J., & Maeng, S. (2018). Age-related decrease in stress responsiveness and proactive coping in male mice. Frontiers in Aging Neuroscience, 10, 128. https://doi.org/10.3389/fnagi.2018.00128
  • Oitzl, M. S., & de Kloet, E. R. (1992). Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning. Behavioral Neuroscience, 106(1), 62–71. https://doi.org/10.1037//0735-7044.106.1.62
  • Oitzl, M. S., van Haarst, A. D., Sutanto, W., & de Kloet, E. R. (1995). Corticosterone, brain mineralocorticoid receptors (MRs) and the activity of the hypothalamic-pituitary-adrenal (HPA) axis: The Lewis rat as an example of increased central MR capacity and a hyporesponsive HPA axis. Psychoneuroendocrinology, 20(6), 655–675. https://doi.org/10.1016/0306-4530(95)00003-7
  • Olijslagers, J. E., de Kloet, E. R., Elgersma, Y., van Woerden, G. M., Joëls, M., & Karst, H. (2008). Rapid changes in hippocampal CA1 pyramidal cell function via pre- as well as postsynaptic membrane mineralocorticoid receptors. The European Journal of Neuroscience, 27(10), 2542–2550. https://doi.org/10.1111/j.1460-9568.2008.06220.x
  • Ong, G. S. Y., & Young, M. J. (2017). Mineralocorticoid regulation of cell function: The role of rapid signalling and gene transcription pathways. Journal of Molecular Endocrinology, 58(1), R33–R57. https://doi.org/10.1530/JME-15-0318
  • Oster, H., Challet, E., Ott, V., Arvat, E., de Kloet, E. R., Dijk, D.-J., Lightman, S., Vgontzas, A., & Van Cauter, E. (2017). The functional and clinical significance of the 24-hour rhythm of circulating glucocorticoids. Endocrine Reviews, 38(1), 3–45. https://doi.org/10.1210/er.2015-1080
  • Otte, C., Hinkelmann, K., Moritz, S., Yassouridis, A., Jahn, H., Wiedemann, K., & Kellner, M. (2010). Modulation of the mineralocorticoid receptor as add-on treatment in depression: A randomized, double-blind, placebo-controlled proof-of-concept study. Journal of Psychiatric Research, 44(6), 339–346. https://doi.org/10.1016/j.jpsychires.2009.10.006
  • Otte, C., Muhtz, C., Daneshkhah, S., Yassouridis, A., Kiefer, F., Wiedemann, K., & Kellner, M. (2006). Mineralocorticoid receptor function in posttraumatic stress disorder after pretreatment with metyrapone. Biological Psychiatry, 60(7), 784–787. https://doi.org/10.1016/j.biopsych.2006.01.014
  • Otte, C., Wingenfeld, K., Kuehl, L. K., Richter, S., Regen, F., Piber, D., & Hinkelmann, K. (2015). Cognitive function in older adults with major depression: Effects of mineralocorticoid receptor stimulation. Journal of Psychiatric Research, 69, 120–125. https://doi.org/10.1016/j.jpsychires.2015.08.001
  • Otte, C., Wingenfeld, K., Kuehl, L. K., Kaczmarczyk, M., Richter, S., Quante, A., Regen, F., Bajbouj, M., Zimmermann-Viehoff, F., Wiedemann, K., & Hinkelmann, K. (2015). Mineralocorticoid receptor stimulation improves cognitive function and decreases cortisol secretion in depressed patients and healthy individuals. Neuropsychopharmacology, 40(2), 386–393. https://doi.org/10.1038/npp.2014.181
  • Ozacmak, H. S., Ozacmak, V. H., Barut, F., Araslı, M., & Ucan, B. H. (2014). Pretreatment with mineralocorticoid receptor blocker reduces intestinal injury induced by ischemia and reperfusion: Involvement of inhibition of inflammatory response, oxidative stress, nuclear factor κB, and inducible nitric oxide synthase. The Journal of Surgical Research, 191(2), 350–361. https://doi.org/10.1016/j.jss.2014.04.040
  • Parker, B. M., Wertz, S. L., Pollard, C. M., Desimine, V. L., Maning, J., McCrink, K. A., & Lymperopoulos, A. (2018). Novel insights into the crosstalk between mineralocorticoid receptor and G protein-coupled receptors in heart adverse remodeling and disease. International Journal of Molecular Sciences, 19(12), 3764. https://doi.org/10.3390/ijms19123764
  • Pascual-Le Tallec, L., & Lombès, M. (2005). The mineralocorticoid receptor: A journey exploring its diversity and specificity of action. Molecular Endocrinology (Baltimore, Md.), 19(9), 2211–2221. https://doi.org/10.1210/me.2005-0089
  • Patel, P. D., Lopez, J. F., Lyons, D. M., Burke, S., Wallace, M., & Schatzberg, A. F. (2000). Glucocorticoid and mineralocorticoid receptor mRNA expression in squirrel monkey brain. Journal of Psychiatric Research, 34(6), 383–392. https://doi.org/10.1016/s0022-3956(00)00035-2
  • Patel, P. D., Sherman, T. G., Goldman, D. J., & Watson, S. J. (1989). Molecular cloning of a mineralocorticoid (type I) receptor complementary DNA from rat hippocampus. Molecular Endocrinology (Baltimore, Md.), 3(11), 1877–1885. https://doi.org/10.1210/mend-3-11-1877
  • Paul, S. N., Wingenfeld, K., Otte, C., & Meijer, O. C. (2022). Brain mineralocorticoid receptor in health and disease: From molecular signalling to cognitive and emotional function. British Journal of Pharmacology, 179(13), 3205–3219. https://doi.org/10.1111/bph.15835
  • Penning, T. M. (2003). Hydroxysteroid dehydrogenases and pre-receptor regulation of steroid hormone action. Human Reproduction Update, 9(3), 193–205. https://doi.org/10.1093/humupd/dmg022
  • Penning, T. M., Jin, Y., Rizner, T. L., & Bauman, D. R. (2008). Pre-receptor regulation of the androgen receptor. Molecular and Cellular Endocrinology, 281(1-2), 1–8. https://doi.org/10.1016/j.mce.2007.10.008
  • Ponti, G., Obernier, K., & Alvarez-Buylla, A. (2013). Lineage progression from stem cells to new neurons in the adult brain ventricular-subventricular zone. Cell Cycle (Georgetown, Tex.), 12(11), 1649–1650. https://doi.org/10.4161/cc.24984
  • Popoli, M., Yan, Z., McEwen, B. S., & Sanacora, G. (2011). The stressed synapse: The impact of stress and glucocorticoids on glutamate transmission. Nature Reviews. Neuroscience, 13(1), 22–37. https://doi.org/10.1038/nrn3138
  • Qi, X.-R., Kamphuis, W., Wang, S., Wang, Q., Lucassen, P. J., Zhou, J.-N., & Swaab, D. F. (2013). Aberrant stress hormone receptor balance in the human prefrontal cortex and hypothalamic paraventricular nucleus of depressed patients. Psychoneuroendocrinology, 38(6), 863–870. https://doi.org/10.1016/j.psyneuen.2012.09.014
  • Qing, L., Liu, L., Zhou, L., Zhang, F., Gao, C., Hu, L., & Nie, S. (2020). Sex-dependent association of mineralocorticoid receptor gene (NR3C2) DNA methylation and schizophrenia. Psychiatry Research, 292, 113318. https://doi.org/10.1016/j.psychres.2020.113318
  • Qiu, S., Champagne, D. L., Peters, M., Catania, E. H., Weeber, E. J., Levitt, P., & Pimenta, A. F. (2010). Loss of limbic system-associated membrane protein leads to reduced hippocampal mineralocorticoid receptor expression, impaired synaptic plasticity, and spatial memory deficit. Biological Psychiatry, 68(2), 197–204. https://doi.org/10.1016/j.biopsych.2010.02.013
  • Quevedo, J., Carvalho, A. F., & Zarate, C. A. (2019). Neurobiology of Depression: Road to Novel Therapeutics. Academic Press.
  • Quinkler, M., Diederich, S., Bähr, V., & Oelkers, W. (2004). The role of progesterone metabolism and androgen synthesis in renal blood pressure regulation. Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones et Metabolisme, 36(6), 381–386. https://doi.org/10.1055/s-2004-814572
  • Rao, R., & Androulakis, I. P. (2019). The physiological significance of the circadian dynamics of the HPA axis: Interplay between circadian rhythms, allostasis and stress resilience. Hormones and Behavior, 110, 77–89. https://doi.org/10.1016/j.yhbeh.2019.02.018
  • Ravid, J. D., & Laffin, L. J. (2022). Effects of finerenone, a novel nonsteroidal mineralocorticoid receptor antagonist, on cardiovascular disease, chronic kidney disease, and blood pressure. Current Cardiology Reports, 24(10), 1251–1259. https://doi.org/10.1007/s11886-022-01750-0
  • Reul, J. M. H. M., & de Kloet, E. R. (1985). Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology, 117(6), 2505–2511. https://doi.org/10.1210/endo-117-6-2505
  • Reul, J. M. H. M., Gesing, A., Droste, S., Stec, I. S. M., Weber, A., Bachmann, C., Bilang-Bleuel, A., Holsboer, F., & Linthorst, A. C. E. (2000). The brain mineralocorticoid receptor: Greedy for ligand, mysterious in function. European Journal of Pharmacology, 405(1-3), 235–249. https://doi.org/10.1016/s0014-2999(00)00677-4
  • Rivers, C., Flynn, A., Qian, X., Matthews, L., Lightman, S., Ray, D., & Norman, M. (2009). Characterization of conserved tandem donor sites and intronic motifs required for alternative splicing in corticosteroid receptor genes. Endocrinology, 150(11), 4958–4967. https://doi.org/10.1210/en.2009-0346
  • Robertson, N. M., Schulman, G., Karnik, S., Alnemri, E., & Litwack, G. (1993). Demonstration of nuclear translocation of the mineralocorticoid receptor (MR) using an anti-MR antibody and confocal laser scanning microscopy. Molecular Endocrinology (Baltimore, Md.), 7(9), 1226–1239. https://doi.org/10.1210/mend.7.9.8247024
  • Rodriguez, J. J., Montaron, M. F., Petry, K. G., Aurousseau, C., Marinelli, M., Premier, S., Rougon, G., Moal, M. L., & Abrous, D. N. (1998). Complex regulation of the expression of the polysialylated form of the neuronal cell adhesion molecule by glucocorticoids in the rat hippocampus. The European Journal of Neuroscience, 10(9), 2994–3006. https://doi.org/10.1046/j.1460-9568.1998.00316.x
  • Roozendaal, B., Bohus, B., & McGaugh, J. L. (1996). Dose-dependent suppression of adrenocortical activity with metyrapone: Effects on emotion and memory. Psychoneuroendocrinology, 21(8), 681–693. https://doi.org/10.1016/s0306-4530(96)00028-5
  • Roozendaal, B., McReynolds, J. R., Van der Zee, E. A., Lee, S., McGaugh, J. L., & McIntyre, C. K. (2009). Glucocorticoid effects on memory consolidation depend on functional interactions between the medial prefrontal cortex and basolateral amygdala. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 29(45), 14299–14308. https://doi.org/10.1523/JNEUROSCI.3626-09.2009
  • Rozeboom, A. M., Akil, H., & Seasholtz, A. F. (2007). Mineralocorticoid receptor overexpression in forebrain decreases anxiety-like behavior and alters the stress response in mice. Proceedings of the National Academy of Sciences of the United States of America, 104(11), 4688–4693. https://doi.org/10.1073/pnas.0606067104
  • Ruhs, S., Nolze, A., Hübschmann, R., & Grossmann, C. (2017). 30 Years Of The Mineralocorticoid Receptor: Nongenomic effects via the mineralocorticoid receptor. Journal of Endocrinology, 234(1), T107–T124. https://doi.org/10.1530/JOE-16-0659
  • Sajadi, A. A., Samaei, S. A., & Rashidy-Pour, A. (2006). Intra-hippocampal microinjections of anisomycin did not block glucocorticoid-induced impairment of memory retrieval in rats: An evidence for non-genomic effects of glucocorticoids. Behavioural Brain Research, 173(1), 158–162. https://doi.org/10.1016/j.bbr.2006.06.018
  • Šalamon Arčan, I., Kouter, K., & Videtič Paska, A. (2022). Depressive disorder and antidepressants from an epigenetic point of view. World Journal of Psychiatry, 12(9), 1150–1168. https://doi.org/10.5498/wjp.v12.i9.1150
  • Sarabdjitsingh, R. A., Joëls, M., & de Kloet, E. R. (2012). Glucocorticoid pulsatility and rapid corticosteroid actions in the central stress response. Physiology & Behavior, 106(1), 73–80. https://doi.org/10.1016/j.physbeh.2011.09.017
  • Schumacher, M. (1990). Rapid membrane effects of steroid hormones: An emerging concept in neuroendocrinology. Trends in Neurosciences, 13(9), 359–362. https://doi.org/10.1016/0166-2236(90)90016-4
  • Schwabe, L., Tegenthoff, M., Höffken, O., & Wolf, O. T. (2013). Mineralocorticoid receptor blockade prevents stress-induced modulation of multiple memory systems in the human brain. Biological Psychiatry, 74(11), 801–808. https://doi.org/10.1016/j.biopsych.2013.06.001
  • Shea, A., Walsh, C., MacMillan, H., & Steiner, M. (2005). Child maltreatment and HPA axis dysregulation: Relationship to major depressive disorder and post traumatic stress disorder in females. Psychoneuroendocrinology, 30(2), 162–178. https://doi.org/10.1016/j.psyneuen.2004.07.001
  • Shekhtman, E., Geerling, J. C., & Loewy, A. D. (2007). Aldosterone-sensitive neurons of the nucleus of the solitary tract: Multisynaptic pathway to the nucleus accumbens. The Journal of Comparative Neurology, 501(2), 274–289. https://doi.org/10.1002/cne.21245
  • Sheppard, K. E. (2002). Nuclear receptors. II. Intestinal corticosteroid receptors. American Journal of Physiology. Gastrointestinal and Liver Physiology, 282(5), G742–746. https://doi.org/10.1152/ajpgi.00531.2001
  • Smythe, J. W., Murphy, D., Timothy, C., & Costall, B. (1997). Hippocampal Mineralocorticoid, but Not Glucocorticoid, Receptors Modulate Anxiety-Like Behavior in Rats. Pharmacology, Biochemistry, and Behavior, 56(3), 507–513. https://doi.org/10.1016/s0091-3057(96)00244-4
  • Sonino, N., Tomba, E., Genesia, M. L., Bertello, C., Mulatero, P., Veglio, F., Fava, G. A., & Fallo, F. (2011). Psychological assessment of primary aldosteronism: A controlled study. The Journal of Clinical Endocrinology and Metabolism, 96(6), E878–883. https://doi.org/10.1210/jc.2010-2723
  • Sousa, N., Paula-Barbosa, M. M., & Almeida, O. F. (1999). Ligand and subfield specificity of corticoid-induced neuronal loss in the rat hippocampal formation. Neuroscience, 89(4), 1079–1087. https://doi.org/10.1016/s0306-4522(98)00311-x
  • Spijker, A. T., & van Rossum, E. F. C. (2009). Glucocorticoid receptor polymorphisms in major depression. Focus on glucocorticoid sensitivity and neurocognitive functioning. Annals of the New York Academy of Sciences, 1179, 199–215. https://doi.org/10.1111/j.1749-6632.2009.04985.x
  • Syed, S. B., & Qureshi, M. A. (2012). Association of aldosterone and cortisol with cardiovascular risk factors in prehypertension stage. International Journal of Hypertension, 2012, 906327. https://doi.org/10.1155/2012/906327
  • ter Horst, J. P., Carobrez, A. P., van der Mark, M. H., de Kloet, E. R., & Oitzl, M. S. (2012). Sex differences in fear memory and extinction of mice with forebrain-specific disruption of the mineralocorticoid receptor. The European Journal of Neuroscience, 36(8), 3096–3102. https://doi.org/10.1111/j.1460-9568.2012.08237.x
  • ter Horst, J. P., van der Mark, M. H., Arp, M., Berger, S., de Kloet, E. R., & Oitzl, M. S. (2012). Stress or no stress: Mineralocorticoid receptors in the forebrain regulate behavioral adaptation. Neurobiology of Learning and Memory, 98(1), 33–40. https://doi.org/10.1016/j.nlm.2012.04.006
  • Torchia, J., Glass, C., & Rosenfeld, M. G. (1998). Co-activators and co-repressors in the integration of transcriptional responses. Current Opinion in Cell Biology, 10(3), 373–383. https://doi.org/10.1016/s0955-0674(98)80014-8
  • van der Heijden, C. D. C. C., Bode, M., Riksen, N. P., & Wenzel, U. O. (2022). The role of the mineralocorticoid receptor in immune cells in cardiovascular disease. British Journal of Pharmacology, 179(13), 3135–3151. https://doi.org/10.1111/bph.15782
  • van Haarst, A. D., Oitzl, M. S., & de Kloet, E. R. (1997). Facilitation of feedback inhibition through blockade of glucocorticoid receptors in the hippocampus. Neurochemical Research, 22(11), 1323–1328. https://doi.org/10.1023/a:1022010904600
  • van Leeuwen, N., Kumsta, R., Entringer, S., de Kloet, E. R., Zitman, F. G., DeRijk, R. H., & Wüst, S. (2010). Functional mineralocorticoid receptor (MR) gene variation influences the cortisol awakening response after dexamethasone. Psychoneuroendocrinology, 35(3), 339–349. https://doi.org/10.1016/j.psyneuen.2009.07.006
  • Viengchareun, S., Le Menuet, D., Martinerie, L., Munier, M., Tallec, L. P.-L., & Lombès, M. (2007). The Mineralocorticoid Receptor: Insights into its Molecular and (Patho)Physiological Biology. Nuclear Receptor Signaling, 5(1), nrs.05012. https://doi.org/10.1621/nrs.05012
  • Viho, E. M. G., Buurstede, J. C., Berkhout, J. B., Mahfouz, A., & Meijer, O. C. (2022). Cell type specificity of glucocorticoid signaling in the adult mouse hippocampus. Journal of Neuroendocrinology, 34(2), e13072. https://doi.org/10.1111/jne.13072
  • Vinkers, C. H., Joëls, M., Milaneschi, Y., Gerritsen, L., Kahn, R. S., Penninx, B. W. J. H., & Boks, M. P. M. (2015). Mineralocorticoid receptor haplotypes sex-dependently moderate depression susceptibility following childhood maltreatment. Psychoneuroendocrinology, 54, 90–102. https://doi.org/10.1016/j.psyneuen.2015.01.018
  • Vogel, S., Klumpers, F., Schröder, T. N., Oplaat, K. T., Krugers, H. J., Oitzl, M. S., Joëls, M., Doeller, C. F., & Fernández, G. (2017). Stress induces a shift towards striatum-dependent stimulus-response learning via the mineralocorticoid receptor. Neuropsychopharmacology : official Publication of the American College of Neuropsychopharmacology, 42(6), 1262–1271. https://doi.org/10.1038/npp.2016.262
  • Wang, C.-H., Hung, P.-W., Chiang, C.-W., Lombès, M., Chen, C.-H., Lee, K.-H., Lo, Y.-C., Wu, M.-H., Chang, W.-C., & Lin, D.-Y. (2019). Identification of two independent SUMO-interacting motifs in Fas-associated factor 1 (FAF1): Implications for mineralocorticoid receptor (MR)-mediated transcriptional regulation. Biochimica et Biophysica Acta. Molecular Cell Research, 1866(8), 1282–1297. https://doi.org/10.1016/j.bbamcr.2019.03.014
  • Wang, Q., Anzick, S., Richter, W. F., Meltzer, P., & Simons, S. S. (2004). Modulation of transcriptional sensitivity of mineralocorticoid and estrogen receptors. The Journal of Steroid Biochemistry and Molecular Biology, 91(4-5), 197–210. https://doi.org/10.1016/j.jsbmb.2004.04.007
  • Watzka, M., Beyenburg, S., Blümcke, I., Elger, C. E., Bidlingmaier, F., & Stoffel-Wagner, B. (2000). Expression of mineralocorticoid and glucocorticoid receptor mRNA in the human hippocampus. Neuroscience Letters, 290(2), 121–124. https://doi.org/10.1016/s0304-3940(00)01325-2
  • Weber, M., Wehling, M., & Lösel, R. (2008). Proteins interact with the cytosolic mineralocorticoid receptor depending on the ligand. American Journal of Physiology. Heart and Circulatory Physiology, 295(1), H361–365. https://doi.org/10.1152/ajpheart.00825.2007
  • Wehling, M. (2005). Effects of Aldosterone and Mineralocorticoid Receptor Blockade on Intracellular Electrolytes. Heart Failure Reviews, 10(1), 39–46. https://doi.org/10.1007/s10741-005-2347-z
  • Wehr, M. C., Hinrichs, W., Brzózka, M. M., Unterbarnscheidt, T., Herholt, A., Wintgens, J. P., Papiol, S., Soto-Bernardini, M. C., Kravchenko, M., Zhang, M., Nave, K., Wichert, S. P., Falkai, P., Zhang, W., Schwab, M. H., & Rossner, M. J. (2017). Spironolactone is an antagonist of NRG1-ERBB4 signaling and schizophrenia-relevant endophenotypes in mice. EMBO Molecular Medicine, 9(10), 1448–1462. https://doi.org/10.15252/emmm.201707691
  • Weikum, E. R., Liu, X., & Ortlund, E. A. (2018). The nuclear receptor superfamily: A structural perspective. Protein Science : a Publication of the Protein Society, 27(11), 1876–1892. https://doi.org/10.1002/pro.3496
  • Wickert, L., Watzka, M., Bolkenius, U., Bidlingmaier, F., & Ludwig, M. (1998). Mineralocorticoid receptor splice variants in different human tissues. European Journal of Endocrinology, 138(6), 702–704. https://doi.org/10.1530/eje.0.1380702
  • Wilson, P., Morgan, J., Funder, J. W., Fuller, P. J., & Young, M. J. (2009). Mediators of mineralocorticoid receptor-induced profibrotic inflammatory responses in the heart. Clinical Science (London, England : 1979), 116(9), 731–739. https://doi.org/10.1042/CS20080247
  • Wingenfeld, K., Kuehl, L. K., Janke, K., Hinkelmann, K., Dziobek, I., Fleischer, J., Otte, C., & Roepke, S. (2014). Enhanced emotional empathy after mineralocorticoid receptor stimulation in women with borderline personality disorder and healthy women. Neuropsychopharmacology : official Publication of the American College of Neuropsychopharmacology, 39(8), 1799–1804. https://doi.org/10.1038/npp.2014.36
  • Wingenfeld, K., & Otte, C. (2019). Mineralocorticoid receptor function and cognition in health and disease. Psychoneuroendocrinology, 105, 25–35. https://doi.org/10.1016/j.psyneuen.2018.09.010
  • Wingenfeld, K., & Wolf, O. T. (2015). Effects of cortisol on cognition in major depressive disorder, posttraumatic stress disorder and borderline personality disorder—2014 Curt Richter Award Winner. Psychoneuroendocrinology, 51, 282–295. https://doi.org/10.1016/j.psyneuen.2014.10.009
  • Wu, T.-C., Chen, H.-T., Chang, H.-Y., Yang, C.-Y., Hsiao, M.-C., Cheng, M.-L., & Chen, J.-C. (2013). Mineralocorticoid receptor antagonist spironolactone prevents chronic corticosterone induced depression-like behavior. Psychoneuroendocrinology, 38(6), 871–883. https://doi.org/10.1016/j.psyneuen.2012.09.011
  • Xing, G.-Q., Russell, S., Webster, M. J., & Post, R. M. (2004). Decreased expression of mineralocorticoid receptor mRNA in the prefrontal cortex in schizophrenia and bipolar disorder. The International Journal of Neuropsychopharmacology, 7(2), 143–153. https://doi.org/10.1017/S1461145703004000
  • Yang, J., & Young, M. J. (2009). The mineralocorticoid receptor and its coregulators. Journal of Molecular Endocrinology, 43(2), 53–64. https://doi.org/10.1677/JME-09-0031
  • Yau, J. L., Noble, J., & Seckl, J. R. (1999). Continuous blockade of brain mineralocorticoid receptors impairs spatial learning in rats. Neuroscience Letters, 277(1), 45–48. https://doi.org/10.1016/s0304-3940(99)00858-7
  • Yiallouris, A., Tsioutis, C., Agapidaki, E., Zafeiri, M., Agouridis, A. P., Ntourakis, D., & Johnson, E. O. (2019). Adrenal aging and its implications on stress responsiveness in humans. Frontiers in Endocrinology, 10, 54. https://doi.org/10.3389/fendo.2019.00054
  • Yokota, K., Shibata, H., Kurihara, I., Kobayashi, S., Suda, N., Murai-Takeda, A., Saito, I., Kitagawa, H., Kato, S., Saruta, T., & Itoh, H. (2007). Coactivation of the N-terminal transactivation of mineralocorticoid receptor by Ubc9. The Journal of Biological Chemistry, 282(3), 1998–2010. https://doi.org/10.1074/jbc.M607741200
  • Young, E. A., Haskett, R. F., Grunhaus, L., Pande, A., Weinberg, V. M., Watson, S. J., & Akil, H. (1994). Increased evening activation of the hypothalamic-pituitary-adrenal axis in depressed patients. Archives of General Psychiatry, 51(9), 701–707. https://doi.org/10.1001/archpsyc.1994.03950090033005
  • Zajkowska, Z., Gullett, N., Walsh, A., Zonca, V., Pedersen, G. A., Souza, L., Kieling, C., Fisher, H. L., Kohrt, B. A., & Mondelli, V. (2022). Cortisol and development of depression in adolescence and young adulthood – a systematic review and meta-analysis. Psychoneuroendocrinology, 136, 105625. https://doi.org/10.1016/j.psyneuen.2021.105625
  • Zandifar, A., Badrfam, R., Sanjari Moghaddam, H., & Akhondzadeh, S. (2022). Efficacy of spironolactone as an adjunctive therapy to risperidone to improve symptoms of schizophrenia: a double-blind, randomized, placebo-controlled, clinical trial. Iranian Journal of Psychiatry, 17(1), 14–23. https://doi.org/10.18502/ijps.v17i1.8045
  • Zennaro, M.-C., Keightley, M.-C., Kotelevtsev, Y., Conway, G. S., Soubrier, F., & Fuller, P. J. (1995). Human mineralocorticoid receptor genomic structure and identification of expressed isoforms. The Journal of Biological Chemistry, 270(36), 21016–21020. https://doi.org/10.1074/jbc.270.36.21016
  • Zhe, D., Fang, H., & Yuxiu, S. (2008). Expressions of hippocampal Mineralocorticoid Receptor (MR) and Glucocorticoid Receptor (GR) in the single-prolonged stress-rats. Acta Histochemica et Cytochemica, 41(4), 89–95. https://doi.org/10.1267/ahc.08013
  • Zhou, M., Bakker, E. H. M., Velzing, E. H., Berger, S., Oitzl, M., Joëls, M., & Krugers, H. J. (2010). Both mineralocorticoid and glucocorticoid receptors regulate emotional memory in mice. Neurobiology of Learning and Memory, 94(4), 530–537. https://doi.org/10.1016/j.nlm.2010.09.005
  • Zhou, M., Kindt, M., Joëls, M., & Krugers, H. J. (2011). Blocking mineralocorticoid receptors prior to retrieval reduces contextual fear memory in mice. PloS One, 6(10), e26220. https://doi.org/10.1371/journal.pone.0026220