EXACERBATION OF APOPTOSIS IN THE DENTATE GYRUS OF THE AGED RAT BY DEXAMETHASONE AND THE PROTECTIVE ROLE OF CORTICOSTERONE

Glucocorticoid-induced cell loss in the dentate gyrus of rats of vario us ages was studied using the TUNEL procedure to detect apoptotic cell s. A highly significant increase in the incidence of apoptosis was obs erved within the dentate hilus and granule cell layer within 24 h of a single injection of dexamethasone (DEX) in rats aged between 1 and 36 months; DEX-induced apoptosis was more pronounced with increasing age . Corticosterone (CORT) did not cause an increase in the rate of apopt osis above that found in age-matched controls. However, CORT pretreatm ent (3 h) resulted in a significantly attenuated DEX-induced apoptosis in both areas of the dentate gyrus. Serum CORT levels in saline-treat ed rats peaked at 6 months of age and reached a nadir at 36 months of age. The results indicate that (i) aged subjects are more susceptible to DEX in terms of dentate gyrus cell loss by apoptosis, () CORT, whic h binds to Type I corticosteroid receptors with a high affinity, might serve to protect against the damaging effects of DEX which is a ligan d of the Type II glucocorticoid receptor, and (iii) declining endogeno us levels of CORT may increase the vulnerability of the dentate gyrus of aged rats to insult by DEX. (C) 1996 Academic Press, Inc.