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GLUCOCORTICOIDS REGULATE THE SYNTHESIS OF GFAP IN INTACT AND ADRENALECTOMIZED RATS BUT DO NOT AFFECT ITS EXPRESSION FOLLOWING BRAIN INJURY
Citation:
O'Callaghan, J., R. Brinton, AND B. McEwen. GLUCOCORTICOIDS REGULATE THE SYNTHESIS OF GFAP IN INTACT AND ADRENALECTOMIZED RATS BUT DO NOT AFFECT ITS EXPRESSION FOLLOWING BRAIN INJURY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/212 (NTIS PB91243030), 1991.
Description:
We examined the effects of corticosterone (CORT) on the amount of glial fibrillary acidic protein (GFAP) in INTACT, adrenalectomized (ADX) and brain-damaged rats. hort (5 days)- to long-term (4 months) CORT administration by injection, pellet implantation, or in the drinking water decreased GFAP by 20-40& in hippocampus and cortex of INTACT rats. hese effects required CORT levels sufficient to cause involution of the thymus. DX caused elevations (50-125%) in hippocampus and cortex GFAP amount within 12 days of surgery that persisted for at least 4 months. ORT replacement of ADX rats decreased GFAP amount in hippocampus and cortex. he effects of long-term CORT and ADX on GFAP in hippocampus and cortex were also seen in striatum, midbrain and cerebellum, findings suggestive of brainwide adrenal steroid regulation of this astrocyte protein. he changes in GFAP amount due to CORT and ADX were paralleled by changes in GFAP and mRNA, indicating a possible transcriptional or at least genomic effect of adrenal steroids. ORT treatment and ADX did not affect in the same way the amount of two other astrocyte proteins: lutamine synthetase activity was unaffected. ajor neuronal structural proteins (p38 or synaptophysin, NF-200, actin, alpha tubulin, beta tubulin and microtubule associated protein-2) were unaffected by CORT and ADX. he negative regulation of GFAP by adrenal steroids suggested that injury-induced increases in GFAP may be attenuated by glucocorticoids. owever, chronic CORT treatment of INTACT rats did not reverse or reduce the large increases in GFAP caused by trauma- or toxicant-induced brain damage. n contrast, CORT treatment begun in 2 week ADX rats, after an increase in GFAP amount had time to occur, did reverse the ADX-induced increase in GFAP. his suggests that ADX-induced cell loss or damage was not the cause of the ADX-induced increase in GFAP. ogether, these data are consistent with a role of astrocytes in mediating the neuroimmune response.