Transient Forebrain Ischemia Induces Differential Bdnf Transcript Expression and Histone Acetylation Patterns in the Rat Hippocampus

Forebrain ischemia induces delayed, selective neuronal death in hippocampal CA1. It has been established that BDNF (brain-derived neurotrophic factor) is an important factor in ischemic injury. However, the exact mechanism of BDNF expression in the hippocampus after ischemia is unclear. We found that the decrease of BDNF protein expression in hippocampal CA1 was associated with a decrease of Bdnf transcript IV expression in the same region of the rats after ischemia/reperfusion (I/R). In hippocampal CA3 and DG, the results showed increased expression of BDNF protein and transcripts I, IIc, III, IV, VI, and X1. Furthermore, at the Bdnf promoters, I/R led to decreased H3K27ac, increased H3K9ac, and H3K14ac in CA1; increased H3K9ac, H3K14ac, and H3K27ac in CA3; no significant change of H3K9ac, H3K14ac, and H3K27ac in DG. HDAC inhibitor SAHA increased the expression of Bdnf transcripts IV, VI, and X1 in CA1. These findings suggest a potential of modulation Bdnf transcript expression to resolve ischemic brain injury through histone acetylation patterns at the Bdnf promoters.