TREM2 and CD163 Ameliorate Microglia-Mediated Inflammatory Environment in the Aging Brain
Xue Han1, Yu-Jia Liu1, Bin-Wen Liu1
1Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University, Nanjing, 210008, Jiangsu, China.
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.
Insights
Aging brains show increased inflammation and cognitive decline. Key genes TREM2 and CD163 may help by reducing neuroinflammation, potentially protecting learning and memory functions in older adults.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Cognitive functions, particularly learning and memory, decline with age.
- Neuroinflammation, mediated by microglia, is associated with age-related neurodegenerative diseases.
Purpose of the Study:
- To identify age-related genes in the human hippocampus.
- To explore the role of specific genes, TREM2 and CD163, in cognitive aging and neuroinflammation.
Main Methods:
- Analysis of microarray data from cognitively normal controls (GSE11882).
- Gene Ontology (GO) and KEGG pathway analyses of differentially expressed genes (DEGs).
- Construction of a protein-protein interaction (PPI) network and identification of key genes using Cytoscape.
- Validation in aged mice using RT-qPCR and Western blotting.
Main Results:
- 120 DEGs were identified in the aging hippocampus.
- TREM2 and CD163 were identified as key genes potentially beneficial for cognition during aging.
- Upregulation of TREM2 and CD163 mRNA in aged mice was confirmed.
- Increased levels of inflammatory factors IL-1β and IL-6 were observed in aged mice.
Conclusions:
- TREM2 and CD163 may be upregulated in the aging brain to counteract microglial activation-induced inflammation.
- These genes might play a protective role in delaying age-related cognitive decline.
- Findings suggest potential therapeutic targets for age-related cognitive impairment.
