Ahs. Hassan et al., EXACERBATION OF APOPTOSIS IN THE DENTATE GYRUS OF THE AGED RAT BY DEXAMETHASONE AND THE PROTECTIVE ROLE OF CORTICOSTERONE, Experimental neurology, 140(1), 1996, pp. 43-52
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.