Analysis of common
gene expression profiles from three vascular dementia rodent studies indicating
neuroinflammation and microglia specific enrichment
Awasthi Pratistha, Saini Riya, Mishra Arpita and Kumar Gaurav
Res. J. Biotech.; Vol. 20(10); 76-83;
doi: https://doi.org/10.25303/2010rjbt076083; (2025)
Abstract
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.
