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The Journal of Neuroscience, July 9, 2003, 23(14):6013-6022
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c-fos Reduces Corticosterone-Mediated Effects on Neurotrophic Factor Expression in the Rat Hippocampal CA1 Region
A. C. Hansson,1,2 W. Sommer,2 R. Rimondini,2 B. Andbjer,2 I. Strömberg,1 andK. Fuxe1 Departments of 1Neuroscience and 2NEUROTEC, Karolinska Institutet, 171 77 Stockholm, Sweden
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.
Key words: adrenalectomy; basic fibroblast growth factor; brain-derived growth factor; glucocorticoid receptor; mineralocorticoid receptor; immediate early gene; antisense oligodeoxynucleotides; in situ hybridization; rat brain
Received May. 1, 2002; revised Apr. 7, 2003; accepted Apr. 11, 2003.
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