Glucocorticoid endangerment of the hippocampus: tissue, steroid and receptor specificity.
Glucocorticoids (GCs) can damage the hippocampus when exposure is prolonged, as well as impair the capacity of hippocampal neurons to survive various neurological insults. We have recently demonstrated that GCs impair the capacity of primary hippocampal cultures to survive many of these same insults. Using this culture system, we have characterized the features with which the GC corticosterone (CORT) impairs the capacity of these cells to survive the excitotoxin kainic acid. The GC endangerment seems to be mediated by the type II, but not type I corticosteroid receptor. As evidence for type II involvement, endangerment of cells was caused by CORT concentrations in the kilodalton range for the type II receptor, and also by the type II ligand dexamethasone; moreover, the endangerment was blocked by a type II antagonist. In contrast, a type I antagonist was not protective. Cultures contained both type I and II receptors. The effect was GC-specific, as cultures were endangered by CORT, cortisol and dexamethasone, but not by non-GC steroids. GCs did not exacerbate kainic acid damage in cerebeller or hypothalamic cultures, despite the presence of corticosteroid receptors. This agrees with the in vivo data showing that the GC exacerbation of neurological insults is either exclusive to or predominant in the hippocampus.
Packan
D R
DR
Department of Biological Sciences, Stanford University, Calif.
Sapolsky
R M
RM
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000196:embryology; D006854:Hydrocortisone / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology; D009474:Neurons / Q000166:cytology*; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D007608:Kainic Acid; D003345:Corticosterone; D006854:Hydrocortisone