Integrated Analysis of Chromatin and Transcriptomic Profiling of Striatum After Cerebral Hypoperfusion in Mice (ATAC-Seq)
Vascular cognitive impairment (VCI) is a major cause of dementia, characterized by cognitive dysfunction resulting from cerebrovascular disease. Chronic cerebral hypoperfusion (CCH) is a significant contributor to VCI, impacting regions such as the white matter and the hippocampus. Despite the known effects on these areas, the response of the striatum to CCH has been less explored. This study aims to elucidate the molecular and cellular mechanisms underlying striatal dysfunction following CCH. Using a mouse model of bilateral common carotid artery stenosis (BCAS), we observed microglial activation in the striatum, suggesting an inflammatory response. We employed RNA-seq and ATAC-seq to integrate transcriptomic and epigenomic data, identifying changes in gene expression and chromatin accessibility associated with CCH. Our analysis revealed upregulation of immune-related pathways and downregulation of neuronal activity pathways, highlighting distinct regulatory mechanisms in response to hypoperfusion. The results provide insights into the pathogenesis of ischemic brain injury and suggest potential therapeutic targets for VCI. Overall design: In this study, the samples included were striatum tissues from mice subjected to BCAS-induced hypoperfusion and sham-operated control mice. The experimental conditions involved inducing chronic cerebral hypoperfusion to mimic conditions of vascular cognitive impairment. Key variables under investigation included changes in gene expression and chromatin accessibility in the striatum, analyzed through RNA-seq and ATAC-seq. This approach aimed to uncover molecular signatures and epigenetic modifications associated with striatal dysfunction and neuroinflammation following CCH, focusing on the role of microglial activation and immune response pathways.