c-fosReduces Corticosterone-Mediated Effects on Neurotrophic Factor Expression in the Rat Hippocampal CA1 Region

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Abstract
The transcription of neurotrophic factors, i.e., basic fibroblast growth factor (bFGF) and brain-derived neurotrophic factor (BDNF) is regulated by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation despite the lack of a classical glucocorticoid response element in their promoter region.A time course for corticosterone (10 mg/kg, s.c.) in adrenalectomized rats revealed a peak hormone effect at the 4 hr time interval forbFGF(110–204% increase),BDNF(53–67% decrease),GR(53–64% decrease), andMR(34–56% decrease) mRNA levels in all hippocampal subregions usingin situhybridization.c-fosmRNA levels were affected exclusively in the dentate gyrus after 50 min to 2 hr (38–46% decrease).Furthermore, it was evaluated whether corticosterone regulation of these genes depends on interactions with the transcription factor complex activator protein-1.c-fosantisense oligodeoxynucleotides were injected into the dorsal hippocampus of adrenalectomized rats. Corticosterone was given 2 hr later, and the effects on gene expression were measured 4 hr later. In CA1, antisense treatment significantly and selectively enhanced the hormone action on the expression ofbFGF(44% enhanced increase) andBDNF(38% enhanced decrease) versus control oligodeoxynucleotide treatment. In addition, an upregulation ofc-fosexpression (89% increase) was found. There were no effects ofc-fosantisense on hippocampalGRandMRexpression. Thus it seems that a tonicc-fosmechanism exists within CA1, which reducesGR- andMR-mediated effects on expression ofbFGFandBDNF.