Corticosterone actions on the hippocampal brain-derived neurotrophic factor expression are mediated by exon IV promoter.
2006 (English)In: Journal of neuroendocrinology (Print), ISSN 0953-8194, Vol. 18, no 2, 104-114 p.Article in journal (Refereed) Published
Brain-derived neurotrophic factor (BDNF) expression is strongly regulated by adrenocorticosteroids via activated gluco- and mineralocorticoid receptors. Four separate promoters are located upstream of the BDNF noncoding exons I to IV and may thus be involved in adrenocorticosteroid-mediated gene regulation. In adrenalectomised rats, corticosterone (10 mg/kg s.c.) induces a robust down-regulation of both BDNF mRNA and protein levels in the hippocampus peaking at 2-8 h. To study the role of the individual promoters in the corticosterone response, we employed exon-specific riboprobe in situ hybridisation as well as real-time polymerase chain reaction (PCR) in the dentate gyrus. We found a down-regulation, mainly of exon IV and the protein-coding exon V, in nearby all hippocampal subregions, but exon II was only down-regulated in the dentate gyrus. Exon I and exon III transcripts were not affected by corticosterone treatment. The results could be confirmed with real-time PCR in the dentate gyrus. It appears as if the exon IV promoter is the major target for corticosterone-mediated transcriptional regulation of BDNF in the hippocampus.
Place, publisher, year, edition, pages
2006. Vol. 18, no 2, 104-114 p.
Adrenalectomy, Analysis of Variance, Animals, Brain-Derived Neurotrophic Factor/genetics/*metabolism, Corticosterone/blood/*physiology, Down-Regulation, Exons/genetics/*physiology, Gene Expression Regulation/*physiology, Hippocampus/*metabolism, Male, Promoter Regions (Genetics)/*physiology, RNA; Messenger/analysis, Rats, Rats; Sprague-Dawley, Time Factors, Transcription; Genetic/physiology
IdentifiersURN: urn:nbn:se:umu:diva-12294DOI: 10.1111/j.1365-2826.2005.01390.xPubMedID: 16420279OAI: oai:DiVA.org:umu-12294DiVA: diva2:151965