Exploratory Transcriptomic Profiling Reveals the Role of Gut Microbiota in Vascular Dementia

Area of Science:

• Neuroscience
• Microbiology
• Genomics

Background:

• Stroke is a leading cause of cognitive impairment and vascular dementia (VaD).
• The gut microbiome's role in VaD pathogenesis, particularly via trimethylamine-N-oxide (TMAO), is suggested but molecular mechanisms remain unclear.
• Understanding these mechanisms is vital for developing targeted therapies for post-stroke cognitive decline.

Purpose of the Study:

• To investigate the molecular mechanisms by which the gut microbe-dependent TMAO pathway influences the brain following stroke.
• To identify differentially expressed genes and key signaling pathways in the ischemic brain cortex.

Main Methods:

• Comprehensive RNA-sequencing analysis of mouse cerebral cortex at pre-stroke, post-stroke day 1, and post-stroke day 3.
• Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.

Main Results:

• Thousands of differentially expressed genes were identified post-stroke.
• Enriched pathways included neurodegeneration, chemokine signaling, calcium signaling, and IL-17 signaling.
• Upregulated genes involved inflammatory responses (e.g., IL-1β, Cxcl10, Ccl2, S100a8, Lcn2); downregulated genes included neuropeptides and transcription factors (e.g., Hcrt, Npas4, Gata3, Pax7).

Conclusions:

• Elevated plasma TMAO levels alter mRNA expression profiles in ischemic brain tissue.
• Identified pathways provide molecular insights into TMAO-enhanced neuroinflammation after stroke.
• This research offers a foundation for exploring TMAO's role in VaD and potential therapeutic interventions.