Corticosterone actions on the hippocampal brain-derived neurotrophic factor expression are mediated by exon IV promoter.
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.
Hansson
A C
AC
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. anita.hansson@mail.nih.gov
Sommer
W H
WH
Metsis
M
M
Strömberg
I
I
Agnati
L F
LF
Fuxe
K
K
D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood / Q000502:physiology*; D015536:Down-Regulation; D005091:Exons / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014158:Transcription, Genetic / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D003345:Corticosterone