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

Area of Science:

• Neuroscience
• Genetics
• Epigenetics

Background:

• Vascular dementia (VaD) is the second most common dementia type, resulting from reduced cerebral blood supply.
• The precise pathological mechanisms underlying VaD remain largely unknown.
• Understanding genetic and epigenetic changes is crucial for elucidating VaD pathophysiology.

Purpose of the Study:

• To identify candidate genes with altered DNA methylation in the hippocampus of a VaD rat model.
• To explore the functional implications of these methylation changes in VaD.

Main Methods:

• Genome-wide DNA methylation analysis using methylated DNA-binding domain sequencing.
• Induction of a VaD rat model via bilateral common carotid artery occlusion.
• Cognitive function assessment using the radial arm maze test.
• Functional annotation and network analysis of differentially methylated genes (DMGs).

Main Results:

• 1,180 differentially methylated genes (DMGs) were identified in the VaD rat model.
• DMGs were significantly enriched in 10 Gene Ontology biological processes.
• Hypomethylation and increased mRNA expression of vascular endothelial growth factor (VEGFA) were observed in the hippocampus, with VEGFA showing statistical significance.

Conclusions:

• This study identified candidate genes, including VEGFA, associated with hippocampal DNA methylation changes in VaD.
• These findings provide preliminary insights into the epigenetic mechanisms contributing to VaD pathophysiology.
• Further research on these candidate genes may aid in understanding and potentially treating VaD.