Transcriptome Profiling of Hippocampus After Cerebral Hypoperfusion in Mice

Area of Science:

• Neuroscience
• Immunology
• Genomics

Background:

• Chronic cerebral hypoperfusion (CCH) is a key factor in vascular cognitive impairment (VCI) pathogenesis.
• Microglial activation and gray matter damage, particularly in the hippocampus, are observed in CCH, but underlying mechanisms are unclear.

Purpose of the Study:

• To investigate the molecular mechanisms of hippocampus damage in CCH.
• To identify specific cell types and pathways involved in CCH-induced VCI.

Main Methods:

• A mouse model of CCH was created using bilateral common carotid artery stenosis (BCAS).
• Cerebral blood flow, hippocampal pathology, and transcriptome profiles were analyzed using RNA-sequencing (RNA-seq) and qRT-PCR.
• Gene Set Enrichment Analysis (GSEA) and integrative analysis with single-cell RNA-seq data were performed.

Main Results:

• BCAS induced decreased cerebral blood flow, hippocampal neuronal loss, and microglial activation.
• GSEA identified activated interferon-beta signaling and inflammatory immune responses.
• Differentially expressed genes were enriched in microglia (up-regulated) and CA1 pyramidal neurons (down-regulated).

Conclusions:

• CCH triggers specific inflammatory pathways, including interferon-beta signaling, in the hippocampus.
• Microglia and CA1 pyramidal neurons are key cell types involved in the pathogenesis of CCH-induced VCI.
• The generated transcriptomic data provides a valuable resource for future research into VCI therapeutic targets.