Identification and analysis correlation between hub genes and immune cell infiltration related to LPS-induced cognitive impairment

TL;DR

This study identifies key genes and immune cells linked to cognitive impairment caused by inflammation in mice brains.

Contribution

The study introduces five hub genes and immune cell types associated with LPS-induced cognitive impairment in mice.

Findings

102 upregulated and 32 downregulated genes were identified in LPS-treated mice brains.

Immune cell infiltration analysis revealed M1 macrophages and T cells as potential contributors to cognitive impairment.

Five hub genes (Cxcl10, Cxcl12, Cxcr3, Gbp2, Ifih1) showed strong correlations with immune cell infiltration.

Abstract

The occurrence of immunity and inflammation outside the central nervous system frequently results in acute cognitive impairment among elderly patients. However, there is currently a lack of standardized methods for diagnosing acute cognitive impairment. The objective of our study was to identify potential mRNA biomarkers and investigate the pathogenesis of acute cognitive impairment in mice brains.

To analyze changes in hub genes associated with acute cognitive impairment, bioinformatics analysis was performed on the mouse brain injury data of sterile saline control group and lipopolysaccharide (LPS) induced experimental group in Gene Expression Omnibus (GEO). Functional analysis was conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), which facilitated to identify some potential mRNA biomarkers for hub gene expression in mice brains. Additionally, the "CIBERSORT X″ R kit was employed to examine immune cell infiltrations of mice brains in LPS group and saline group.

In the LPS and saline group, 102 significantly upregulated differentially expressed genes (DEGs) and 32 downregulated DEGs were identified. The pathway enrichment analysis using GO and KEGG revealed that these DEGs were mainly related to the regulation of cytokine, cytokine-cytokine receptor interaction, as well as protein interaction with cytokine and cytokine receptor. Immune cell infiltration analysis indicated potential involvement of M1 macrophages, NK cells resting, T cells CD4 memory, and T cells CD8 naive in the process of cognitive impairment. By constructing a protein-protein interaction (PPI) network, five hub genes (Cxcl10, Cxcl12, Cxcr3, Gbp2, and Ifih1) showed significant associations with immune cell types by using a threshold Spearman's rank correlation coefficient of R > 0.50 and p < 0.05.

The mRNA expression profile of the mice brain tissues in the LPS group differed from that in the normal saline group. These significantly expressed mRNAs may act an importance in the pathogenesis of acute cognitive impairment through mechanisms involving immunity and neuroinflammation.

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