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Brain Corticosteroid Receptor Balance in Health and Disease¹

Division of Medical Pharmacology (E.R.D.K., E.V., M.S.O.), Leiden/Amsterdam Center for Drug Research, University of Leiden, 2300 RA Leiden, The Netherlands; and Institute for Neurobiology (M.J.), University of Amsterdam, 1098 SM Amsterdam, The Netherlands

I. Introduction

II. Corticosteroid Receptor Properties

A. Corticosteroid receptor diversity in brain and pituitary

B. Access of corticosteroids to brain receptors

C. Expression of MR, GR, and receptor variants

D. Regulation of transcriptional activity

E. Conclusion

III. Molecular and Cellular Effects of Corticosteroids in Hippocampus

A. Intrinsic cell properties

B. Amino acid transmission

C. Aminergic transmission

D. Chronic absence of corticosterone

E. Chronic exposure to high corticosteroid levels

F. Conclusion

IV. Role of Corticosteroid Receptors in the Central Stress Response

A. Corticosteroid receptors and HPA control

B. Role of hippocampus in HPA regulation

C. Behavioral effects involving hippocampal MR and GR

D. Glucocorticoid feedback resistance and supersensitivity

E. GR knockouts

F. Conclusion

V. Implications for Age- and Stress-Related Brain Disorders

A. Role of genotype

B. Impact of early life experience

C. Corticosteroids and affective disorders

D. Aging, neurodegeneration, and age-related diseases

E. Conclusion

VI. Summary