Identifying the Involvement of Pro-Inflammatory Signal in Hippocampal Gene Expression Changes after Experimental
Galina T Shishkina1, Natalia V Gulyaeva2,3, Dmitriy A Lanshakov1
1Laboratory of Functional Neurogenomics, Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russia.
Biomedicines
|December 24, 2021
Summary
Acute cerebral ischemia triggers hippocampal inflammation. Ten key genes identified may mediate immune cell activation in the brain following stroke, offering insights into inflammatory responses.
Area of Science:
- Neuroscience
- Immunology
- Genomics
Background:
- Acute cerebral ischemia, such as stroke, is known to induce inflammation in distant brain regions like the hippocampus.
- The precise molecular mechanisms driving this distant inflammatory response in the hippocampus following ischemic events remain largely unknown.
Purpose of the Study:
- To identify key molecular players and genomic mechanisms involved in acute hippocampal immune cell activation after experimental focal brain ischemia.
- To compare gene expression profiles in response to ischemic injury versus direct inflammatory stimuli.
Main Methods:
- Comparison of hippocampal gene expression profiles in rats subjected to middle cerebral artery occlusion (MCAO) and intracerebral lipopolysaccharide (LPS) administration.
- Functional annotation clustering, gene ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed.
Main Results:
- Ten specific genes (Clec5a, CD14, Fgr, Hck, Anxa1, Lgals3, Irf1, Lbp, Ptx3, Serping1) were identified as potential key mediators of hippocampal immune cell activation in MCAO.
- These genes clustered within innate immunity-related categories and responded to both MCAO and LPS stimuli.
- LPS-responsive genes were significantly enriched in pathways like "positive regulation of tumor necrosis factor biosynthetic process," "cell adhesion," "TNF signaling pathway," and "phagosome."
- Genes involved in "regulation of cell proliferation" and the "HIF-1 signaling pathway" were more associated with non-LPS-responding genes.
Conclusions:
- The study highlights a set of ten genes crucial for understanding the genomic basis of hippocampal immune activation post-ischemia.
- These findings elucidate molecular links between focal brain ischemia and inflammatory responses in the hippocampus.
- The results contribute to a deeper comprehension of how immune and inflammatory processes impact hippocampal gene expression following ischemic brain injury.
