title: c-fos reduces corticosterone-mediated effects on neurotrophic factor expression in the rat hippocampal CA1 region.
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 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.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. anita.hansson@neuro.ki.se
authors.forename: A C
authors.initials: AC
authors.lastname: Hansson
authors.forename: W
authors.initials: W
authors.lastname: Sommer
authors.forename: R
authors.initials: R
authors.lastname: Rimondini
authors.forename: B
authors.initials: B
authors.lastname: Andbjer
authors.forename: I
authors.initials: I
authors.lastname: Strömberg
authors.forename: K
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003345:Corticosterone / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D015415:Biomarkers; D009414:Nerve Growth Factors; D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003345:Corticosterone