The effects of corticosterone and dehydroepiandrosterone on neurotrophic factor mRNA expression in primary hippocampal and astrocyte cultures

The effects of corticosterone (CORT) and dehydroepiandrosterone (DHEA) on the expression of growth factor mRNA in either primary hippocampal cultures or astrocyte-enriched cultures from E18 CD rats was studied. In mixed primary cultures, 1 muM CORT up-regulated basic fibroblast growth factor (bFGF; FGF2) after 6 h of exposure, but down-regulated nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) were unchanged. A 100 muM NMDA alone decreased NT-3, increased BDNF, but had no effect on NGF or FGF2. Concurrently administered CORT had no additional effect on either NGF, BDNF or NT-3, but up-regulated FGF2. In astrocytic cultures, 1 muM CORT increased FGF2 and NT-3, but decreased BDNF and NGF. A dose-response study confirmed these results. DHEA (100 nM) up-regulated NGF after 3 h, but not at other time points (6, 12, 24, 48 h). It had no effect on the other growth factors in mixed primary cultures. In astrocytic cultures, there was no effect of DHEA. Adding DHEA or its sulphate (up to 1 muM) to CORT did not alter the latter's action on growth factor mRNA expression. These results show that CORT has a selective action on growth factor expression, which was greater in astrocytic than in mixed cultures, that CORT amplifies or moderates activity-induced expression following NMDA, but that DHEA does not influence the effects of CORT on growth factor mRNA expression under these conditions. (C) 2004 Elsevier B.V. All rights reserved.