TREM2 and CD163 Ameliorate Microglia-Mediated Inflammatory Environment in the Aging Brain

J Mol Neurosci. 2022 May;72(5):1075-1084. doi: 10.1007/s12031-022-01965-4. Epub 2022 Mar 19.

Abstract

Aging decreases cognitive functions, especially learning and memory. Neuroinflammation is mediated by microglia and occurs in age-related neurodegenerative diseases. The expression profiles in a dataset of cognitively normal controls (GSE11882) were obtained from the Gene Expression Omnibus (GEO) database. Microarray data were used to explore the expression of age-related genes in the human hippocampus. A total of 120 differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed. A total of 18 key genes were identified by the plugin cytoHubba in Cytoscape software. Two genes with a positive impact on cognition during aging were teased out: triggering receptor expressed on myeloid cells 2 (TREM2) and a scavenger receptor (CD163). Finally, the results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) verified that the mRNA expression of these two genes was significantly upregulated in aged mice. Moreover, the levels of the inflammatory factors IL-1β and IL-6 were significantly increased. TREM2 and CD163 may be upregulated to alleviate the inflammatory environment resulting from microglial activation in the aging brain, thereby delaying cognitive decline.

Keywords: Aging; Bioinformatics; Microglia; Neuroinflammation.

MeSH terms

  • Animals
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Brain
  • Computational Biology / methods
  • Gene Expression Profiling* / methods
  • Membrane Glycoproteins / genetics
  • Mice
  • Microglia*
  • Receptors, Cell Surface
  • Receptors, Immunologic / genetics

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Trem2 protein, mouse