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

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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.

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Availability of Data and Materials

The analysis of datasets generated during the current study are available from the corresponding author on reasonable request.

Abbreviations

TREM2:

Triggering receptor expressed on myeloid cells 2

CD163:

Scavenger receptor

GEO:

Gene Expression Omnibus

DEGs:

Differentially expressed genes

GO:

Gene Ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

PPI:

Protein–protein interaction

AD:

Alzheimer’s disease

DAP12:

DNAX-activating protein of 12 kDa

GSE11882:

Dataset of cognitively normal controls

ADRC:

Alzheimer’s Disease Research Center

MCC:

Maximal clique centrality

MNC:

Maximum neighborhood component

DMNC:

Density of maximum neighborhood component

CC:

Cellular component

BP:

Biological process

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Acknowledgements

The authors of the present study would like to thank their colleagues and the staff members of GEO database.

Funding

This research was supported by the National Natural Science Foundation of China (81730033, 81701371) and the Key Talent’s 13th Five-Year Plan for Strengthening Health of Jiangsu Province of China (ZDRCA2016069).

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Authors and Affiliations

  1. Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University, Nanjing, 210008, Jiangsu, China

    Xue Han, Yu-Jia Liu, Bin-Wen Liu, Zheng-Liang Ma, Tian-Jiao Xia & Xiao-Ping Gu

  2. Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, China

    Tian-Jiao Xia

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  1. Xue Han
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  2. Yu-Jia Liu
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Contributions

Acquisition and analysis of data: Xue Han. Experimental verification: XueHan, Binwen Liu. Citical revision of the manuscript for important intellectual content: Yujia Liu, Tianjiao Xia, Xiaoping Gu. Study supervision: Zhengliang Ma, Tianjiao Xia, Xiaoping Gu.

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Correspondence to Zheng-Liang Ma, Tian-Jiao Xia or Xiao-Ping Gu.

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All animal experiments were approved by the Experimental Animals Welfare and Ethical Inspection of Nanjing Drum Tower Hospital (Nanjing, China) (approval no. 2019AE01077).

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Han, X., Liu, YJ., Liu, BW. et al. TREM2 and CD163 Ameliorate Microglia-Mediated Inflammatory Environment in the Aging Brain. J Mol Neurosci 72, 1075–1084 (2022). https://doi.org/10.1007/s12031-022-01965-4

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