Persistent BDNF exon I–IX mRNA expression following the withdrawal of neuronal activity in neurons

It is still unclear whether an active state of transcription once established in chromatin persists in neurons. Here, we focused on BDNF exon I–IX mRNA expression because of its marked induction upon the treatment of rat cortical neurons with trichostatin A, suggesting strong repression of the expression through histone deacetylase activity. Acetylation of histones H3 and H4 in promoter-I of the BDNF gene (BDNF-PI) was induced by membrane depolarization time- and dose-dependently, corresponding with the increase in mRNA expression. Following withdrawal of the depolarization, the mRNA level remained elevated for at least 6 h, the persistence of which depended upon the strength of depolarization, whereas the BDNF exon IV–IX expression did not. The acetylation of histones was also maintained with BDNF-PI. Thus, BDNF exon I–IX mRNA expression remained increased after depolarization was withdrawn, suggesting that once activated, the BDNF-PI transcription persists due to chromatin remodeling.