c-fos reduces corticosterone-mediated effects on neurotrophic factor expression in the rat hippocampal CA1 region.

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 for bFGF (110-204% increase), BDNF (53-67% decrease), GR (53-64% decrease), and MR (34-56% decrease) mRNA levels in all hippocampal subregions using in situ hybridization. c-fos mRNA 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-fos antisense 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 of bFGF (44% enhanced increase) and BDNF (38% enhanced decrease) versus control oligodeoxynucleotide treatment. In addition, an upregulation of c-fos expression (89% increase) was found. There were no effects of c-fos antisense on hippocampal GR and MR expression. Thus it seems that a tonic c-fos mechanism exists within CA1, which reduces GR- and MR-mediated effects on expression of bFGF and BDNF.