Hostname: page-component-745bb68f8f-d8cs5 Total loading time: 0 Render date: 2025-01-26T19:45:08.465Z Has data issue: false hasContentIssue false
  • English
  • Français

The Vulnerability of the Hippocampus to Protective and Destructive Effects of Glucocorticoids in Relation to Stress

Published online by Cambridge University Press:  06 August 2018

Bruce S. McEwen ,
Elizabeth A. Gould  and
Randall R. Sakai
Bruce S. McEwen
Affiliation:
Laboratory of Neuroendocrinology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Elizabeth A. Gould
Affiliation:
Laboratory of Neuroendocrinology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Randall R. Sakai
Affiliation:
Laboratory of Neuroendocrinology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Get access Rights & Permissions [Opens in a new window]

Extract

The pituitary—adrenal axis participates in the diurnal response of the organism to the environment and in its response to stress. Circulating glucocorticoid and mineralocorticoid hormones act on cells in the brain via Type I and Type II receptors, which operate at the level of gene regulation, and mediate various feedback effects of adrenal steroids on brain chemistry and structure, including the operation of second-messenger generating systems, levels of structural proteins of glial cells, and the death and survival of neurons. The hippocampus is prominent in these effects, and it also displays the highest level of Type I receptors of any brain region. New concepts point to a special role of the hippocampus, a nexus of cognition and emotion, in the feedback actions of adrenal steroids during the diurnal rhythm, and in response to stress. The hippocampus is, therefore, a prime target area for investigation of the events which accompany stress, and which may be related to the maladaptive state that results in depressive illness. Initial studies are described which investigate the effects of tianeptine on pituitary—adrenal function, hippocampal morphology and Type I and Type II receptor levels.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 160 , Issue S15: Stress, Serotonin and Tianeptine , February 1992 , pp. 18 - 23
Copyright
Copyright © The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Akana, S., Jacobson, L., Cascio, C., et al (1988) Constant corticosterone replacement normalizes basal adrenocorticotropin (ACTH) but permits sustained ACTH hypersecretion after stress in adrenalectomized rats. Endocrinology, 122, 1337–1342.Google Scholar
Brinton, R. & McEwen, (1988) Regional distinctions in the regulation of type I and type II adrenal steroid receptors in the central nervous system. Neuroscience Research Communications, 2, 37–45.Google Scholar
Chou, Y.-C. & Luttge, W. G. (1988) Activated type II receptors in brain cannot rebind glucocorticoids: relationship to progesterone's antiglucocorticoid actions. Brain Research, 440, 67–78.Google Scholar
Dallman, M., Akana, S., Cascio, C., et al (1987) Regulation of ACTH secretion: variations on a theme of B. Recent Progress in Hormone Research, 43, 113–172.Google Scholar
Edwards, C., Burt, D., McIntyre, M., et al (1988) Localization of 11-beta-hydroxysteroid dehydrogenase-tissue specific protector of the mineralocorticoid receptor. Lancet, ii, 986–989.Google Scholar
Eisen, L. & Harmon, J. (1986) Activation of the rat kidney mineralocorticoid receptor. Endocrinology, 119, 1419–1426.Google Scholar
Funder, J., Pearce, P., Smith, R., et al (1988) Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science, 242, 583–585.Google Scholar
Gannon, M. & McEwen, B. S. (1990) Calmodulin involvement in stress- and corticosterone-induced down-regulation of cyclic AMP generating systems in brain. Journal of Neurochemistry, 55, 276–284 Google Scholar
Gannon, M., Brinton, R., Sakai, R., et al (1991) Diurnal differences and adrenal involvement in calmodulin stimulation of hippocampal adenylate cyclase activity. Journal of Neuroendocrinology, 3, 37–43.Google Scholar
Gold, P., Goodwin, F. & Chrousos, G. (1988a) Clinical and biochemical manifestations of depression. (Part 1). New England Journal of Medicine, 319, 348–353.Google Scholar
Gold, P., Goodwin, F. & Chrousos, G. (1988b) Clinical and biochemical manifestations of depression. (Part 2). New England Journal of Medicine, 319, 413–420.Google Scholar
Gould, E., Woolley, C. & McEwen, B. S. (1990) Short-term glucocorticoid manipulations affect neuronal morphology and survival in the adult dentate gyrus. Neuroscience, 37, 367–375.Google Scholar
Harrelson, A., Rostene, W. & McEwen, B. S. (1987) Adrenocortical steroids modify neurotransmitter-stimulated cyclic AMP accumulation in the hippocampus and limbic brain of the rat. Journal of Neurochemistry, 48, 1648–1655.Google Scholar
Jacobson, L., Akana, S., Cascio, C., et al (1988) Orcadian variations in plasma corticosterone permit normal termination of adrenocorticotropin responses to stress. Endocrinology, 122, 1343–1348.CrossRefGoogle Scholar
McEwen, B. S. (1988) Destructive hormonal influences on brain aging: the result of interacting modulators? In New Trends in Aging Research (eds Pepeu, G., Tominson, B. & Wischik, C.), pp. 75–84. Abano Terme: Fidia.Google Scholar
McEwen, B. S., Weiss, J. & Schwartz, L. (1968) Selective retention of corticosterone by limbic structures in rat brain. Nature, 220, 911–912.Google Scholar
McEwen, B. S., Dekloet, R. & Rostene, W. (1986) Adrenal steroid receptors and actions in the nervous system. Physiological Reviews, 66, 1121–1188.Google Scholar
McEwen, B. S.& Gould, E. (1990) Adrenal steroid influences on the survival of hippocampal neurons. Biochemical Pharmacology, 40, 2393–2402.Google Scholar
McEwen, B. S., Brinton, R., Chao, H., et al (1990) The hippocampus: a site for modulatory interactions between steroid hormones, neurotransmitters and neuropeptides. In Neuroendocrine Perspectives (eds Mullter, E. & MacLeod, R.), pp. 93–131. New York: Springer Verlag.Google Scholar
Mendel, D., Bodwell, J., Gamechu, B., et al (1986) Molybdatestabilized non-activated glucocorticoid-receptor complexes contain a 90-kDa non-steroid-binding phosphoprotein that is lost on activation. Journal of Biological Chemistry, 261, 3758–3763.Google Scholar
Meyer, J. (1985) Biochemical effects of corticosteroids on neural tissues. Physiological Reviews, 65, 946–1020.Google Scholar
Miller, A., Spencer, R., Stein, M., et al (1990) Adrenal steroid receptor binding in spleen and thymus after stress or dexamethasone. American Journal of Physiology, 259, E405–E412.Google Scholar
Munck, A., Guyre, P. & Holbrook, N. (1984) Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocrine Reviews, 5, 25–44.CrossRefGoogle ScholarPubMed
Musacchio, J., Julou, L., Kety, S., et al (1969) Increase in rat brain tyrosine hydroxylase activity produced by electroconvulsive shock. Proceedings of the National Academy of Sciences of the United States of America, 63, 1117–1119.Google Scholar
Ramey, E. & Goldstein, M. (1957) The adrenal cortex and sympathetic nervous system. Physiological Reviews, 37, 155–195.CrossRefGoogle Scholar
Richard, F., Faucon-Biguet, N., Labatut, R., et al (1988) Modulation of tyrosine hydroxylase gene expression in rat brain and adrenals by exposure to cold. Journal of Neuroscience Research, 20, 32–37.Google Scholar
Rostene, W., Fischette, C., Dussaillant, M., et al (1985) Adrenal steroid modulation of vasoactive intestinal peptide effect on serotonin 1 binding sites in the rat brain shown by in vitro quantitative autoradiography. Neuroendocrinology, 40, 129–134.Google Scholar
Sanchez, E., Housley, P. & Pratt, W. (1986) The molybdate stabilized glucocorticoid binding complex of L-cells contains a 98–100 Kdalton steroid binding phosphoprotein and a 90 Kdalton nonsteroid-binding phosphoprotein that is part of the murine hear-shock complex. Journal of Steroid Biochemistry, 24, 9–18.Google Scholar
Sando, J., Hammond, N., Stratford, C., et al (1979) Activation of thymocyte glucocorticoid receptors to the steroid binding form. Journal of Biological Chemistry, 254, 4779–4789.Google Scholar
Sapolsky, R., Krey, L. & McEwen, B. S. (1984) Stress down-regulates corticosterone receptors in a site-specific manner in the brain. Endocrinology, 114, 287–292.Google Scholar
Sapolsky, R., Krey, L. & McEwen, B. S. (1986) The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocrine Reviews, 7, 284–301.Google Scholar
Schmidt, T. & Litwack, G. (1982) Activation of the glucocorticoid-receptor complex. Physiological Reviews, 62, 1131–1192.Google Scholar
Seal, U. & Doe, R. (1966) Corticosteroid-binding globulin: biochemistry, physiology and phylogeny. In Steroid Dynamics (eds Pincus, G., Nakao, T. & Tait, J.), pp. 63–90. New York: Academic Press.Google Scholar
Selye, H. (1973) The evolution of the stress concept. American Scientist, 61, 692–699.Google Scholar
Sloviter, R., Valiquette, G., Abrams, G., et al (1989) Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy. Science, 243, 535–538.Google Scholar
Spencer, R., Young, E., Choo, P., et al (1990) Glucocorticoid type I and type II receptor binding: estimates of in vivo receptor number, occupancy and activation with varying level of steroid. Brain Research, 514, 37–48.Google Scholar
Stone, E., Slucky, A., Platt, J., et al (1985) Reduction of the cyclic adenosine 3'5'-monophosphate response to catecholamines in rat brain slices after repeated restraint stress. Journal of Pharmacology and Experimental Therapeutics, 233, 382–388.Google Scholar
Stone, E., Platt, J., Herrera, A., et al (1986) Effect of repeated restraint stress, desmethylimipramine or adrenocorticotropin on the alpha and beta adrenergic components of the cyclic AMP response to norepinephrine in rat brain slices. Journal of Pharmacology and Experimental Therapeutics, 237, 702–707.Google ScholarPubMed
Stone, E., McEwen, B. S., Herrera, A., et al (1987) Regulation of α and β components of noradrenergic cyclic AMP response in cortical slices. European Journal of Pharmacology, 141, 347–356.Google Scholar
Thoenen, H. (1970) Induction of TH in peripheral and central adrenergic neurons by cold exposure of rats. Nature, 228, 861–862.Google Scholar
Uno, H., Ross, T., Else, J., et al (1989) Hippocampal damage associated with prolonged and fatal stress in primates. Journal of Neuroscience, 9, 1705–1711.Google Scholar
Weiss, J. (1972) Psychological factors in stress and disease. Scientific American, 226, 104–113.Google Scholar
Weiss, J., Goodman, P., Losito, B., et al (1981) Behavioral depression produced by an uncontrollable stressor: relationship to norepinephrine, dopamine and serotonin levels in various regions of rat brain. Brain Research Review, 3, 167–205.Google Scholar
Woolley, C., Gould, C. & McEwen, B. S. (1990) Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Research, 531, 225–231.Google Scholar
Yamamoto, K. (1985) Steroid receptor regulated transcription of specific genes and gene networks. Annual Review of Genetics, 19, 209–252.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.