Analysis of common gene expression profiles from three vascular dementia rodent studies indicating neuroinflammation and microglia specific enrichment

Vascular dementia is characterized by deterioration in an individual's cognitive capacities, such as memory deficits, decreased cognitive processing speed and difficulties in sustaining attention, which necessitate a thorough understanding of its molecular mechanisms. Here, we attempt to investigate pathways, brain-specific mechanisms and predicted drugs using three different transcriptome studies of the BCAS (Bilateral Carotid Artery Stenosis) mice model of VaD. We used the NCBI GEO database for gene expression analysis from three RNA-Seq datasets across the hippocampal and cortex regions of the brains of BCAS mice models and identified differentially expressed genes (DEGs). We further performed functional gene enrichment using DAVID and brain cell type enrichment using Enrichr. Furthermore, a drug prediction was conducted using DGIdb. From the three datasets selected, we identified 980 DEGs (GSE223580), 1,236 DEGs (GSE210666) and 1,231 DEGs (Sang-Ha Baik et al) after filtering the significant LogFc. After filtering them by applying a cutoff of ± 0.4, we found 170 common DEGs. The common DEGs were involved in pathways associated with neuroinflammation, metabolism and cell death related pathways. These DEGs are also significantly enriched in microglial cell type, affirming neuroinflammatory response in the BCAS model. The hub genes associated with the common DEGs model network revealed CD44, TLR2 and ICAM-1also having role in neuroinflammation. The top 2 drugs predicted in this condition include disulfiram and sulfasal. Current analysis reveals a role of neuroinflammation and microglia in vascular dementia pathogenesis and reveals multiple targets that can be experimentally tested.