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 microM 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 microM 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 microM 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 microM) 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.
Department of Anatomy, and Cambridge Centre for Brain Repair, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
E M
EM
Gubba
J W
JW
Fawcett
J
J
Herbert
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D003687:Dehydroepiandrosterone; D003345:Corticosterone