Han Xue, Liu Yu-Jia, Liu Bin-Wen, Ma Zheng-Liang, Xia Tian-Jiao, Gu Xiao-Ping
Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University, Nanjing, 210008, Jiangsu, China.
Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, China.
J Mol Neurosci. 2022 May;72(5):1075-1084. doi: 10.1007/s12031-022-01965-4. Epub 2022 Mar 19.
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.
衰老会降低认知功能，尤其是学习和记忆能力。神经炎症由小胶质细胞介导，发生在与年龄相关的神经退行性疾病中。认知正常对照数据集（GSE11882）中的表达谱是从基因表达综合数据库（GEO）获得的。利用微阵列数据探索人类海马体中与年龄相关基因的表达。共鉴定出120个差异表达基因（DEG），并进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。构建了蛋白质-蛋白质相互作用（PPI）网络。通过Cytoscape软件中的cytoHubba插件鉴定出18个关键基因。筛选出两个在衰老过程中对认知有积极影响的基因：髓样细胞2上表达的触发受体（TREM2）和清道夫受体（CD163）。最后，逆转录-定量聚合酶链反应（RT-qPCR）和蛋白质印迹法（WB）的结果证实，这两个基因的mRNA表达在老年小鼠中显著上调。此外，炎症因子IL-1β和IL-6的水平显著升高。TREM2和CD163可能被上调以减轻衰老大脑中因小胶质细胞激活而产生的炎症环境，从而延缓认知衰退。
