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.