Changes in gene expression in hippocampus in response to glucocorticoids and stress.

Glucocorticoid hormones, acting through two types of intracellular receptors to modulate gene activity, have diverse behavioral, neurochemical and neurodegenerative effects in hippocampus. We have previously cloned hippocampal mRNAs that respond to the endogenous glucocorticoid, corticosterone (CORT): glycerol phosphate dehydrogenase (EC 1.1.1.8; GPDH), an oligodendrocyte marker; CR16, whose sequence is not yet identified; and glial fibrillary acidic protein (GFAP), a marker of astroglial reactivity. In these studies, we have subjected rats to 2 hr vibratory stress as a treatment that raises circulating CORT levels, and analyzed changes in GPDH, CR16 and GFAP mRNAs in rat hippocampus. Only GPDH mRNA responded to stress in intact rats; GPDH mRNA did not respond to the same treatment in rats where the adrenal source of CORT had been removed surgically. The lack of stress responsiveness of CR16 and GFAP mRNAs, despite elevated corticosterone levels, is consistent with their slower (greater than 2 hr but less than 8 hr) response to administered CORT. These studies indicate that temporal aspects of CORT regulation may account in part for differential responses to vibratory stress of CORT-dependent mRNA responses in hippocampus. An increase in GPDH gene activity represents a CORT-dependent stress response that can be used to characterize changes in neuroendocrine status and stress responsiveness of target cells.