DNA methylation of promoter region is thought to be involved in pathogenesis of several diseases. In cerebral ischemia, some studies have reported that infarct volume is decreased by inhibition of DNA methyltransferases (DNMTs) that mediates DNA methylation. However, roles of DNMTs in cerebral ischemia have not been clarified. Therefore, we investigated whether DNA methylation was associated with pathology of cerebral ischemia.
In this study, an in vivo cerebral ischemia was produced by occlusion of middle cerebral artery and reperfusion (MCAO/R) in the rat. First, we investigated protein levels of DNMTs. Protein levels of DNMT3a, but not DNMT3b, were increased in penumbra regions 1 day after MCAO/R compared with those in same regions of sham-operated rats. Also, Immunohistochemical examination 1 day after MCAO/R revealed that DNMT3a-positive cells in penumbra regions were colocalized with NeuN-positive neurons. Therefore, we determined effect of DNMTs inhibitor RG108 against N-methyl-D-aspartate (NMDA)-induced neuronal cell death in primary cultured rat cortical neurons. RG108 protected neurons from NMDA-induced cell death.
These results suggested that neuronal cell death after cerebral ischemia was correlated with DNA methylation by DNMT3a.