Genome-wide DNA methylation profiling in a rat model with vascular dementia

Vascular dementia (VaD), the second most prevalent type of dementia, is caused by reduced blood supply to the brain that results in cognitive impairment. Despite the efforts of numerous studies, the pathological mechanisms behind VaD remain unclear. The aim of the present study was to identify candidate genes that undergo changes in hippocampal DNA methylation owing to VaD. A genome-wide DNA methylation analysis was performed, using methylated DNA-binding domain sequencing. VaD model rats with cognitive impairment induced by bilateral common carotid artery occlusion were confirmed using the radial arm maze test. A total of 1,180 differentially methylated genes (DMGs) were identified, and functional annotation analysis revealed the DMGs to be enriched in 10 Gene Ontology biological processes. Network analysis using the STRING database indicated that seven genes were closely connected. Rats in the VaD model group demonstrated relative hypomethylation in the promoter region and increased mRNA expression of the hippocampal genes vascular endothelial growth factor (VEGFA) and kinase insert domain receptor, but only differences in VEGFA mRNA expression levels were determined to be statistically significant. In conclusion, these preliminary data from the functional annotation of hippocampal DMGs in the promoter region highlighted candidate genes for VaD that may contribute to the elucidation of its pathophysiology.