Activation of microglia and astrocytes, a prominent hallmark of both aging and Alzheimer’s disease (AD), has been suggested to contribute to aging and AD progression, but the underlying cellular and molecular mechanisms are largely unknown. We performed RNA-seq analyses on microglia and astrocytes freshly isolated from wild-type and APP-PS1 (AD) mouse brains at five time points to elucidate their age-related gene-expression profiles. Our results showed that from 4 months onward, a set of age-related genes in microglia and astrocytes exhibited consistent upregulation or downregulation (termed “age-up”/“age-down” genes) relative to their expression at the young-adult stage (2 months). And most age-up genes were more highly expressed in AD mice at the same time points. Bioinformatic analyses revealed that the age-up genes in microglia were associated with the inflammatory response, whereas these genes in astrocytes included widely recognized AD risk genes, genes associated with synaptic transmission or elimination, and peptidase-inhibitor genes. Overall, our RNA-seq data provide a valuable resource for future investigations into the roles of microglia and astrocytes in aging- and amyloid-β-induced AD pathologies.

中文翻译：

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整个衰老过程中小胶质细胞和星形胶质细胞的转录组分析

小胶质细胞和星形胶质细胞的激活，这是衰老和阿尔茨海默氏病（AD）的一个显着特征，已被证明有助于衰老和AD的进展，但基本的细胞和分子机制尚不清楚。我们在五个时间点对从野生型和APP-PS1（AD）小鼠脑新鲜分离出的小胶质细胞和星形胶质细胞进行了RNA-seq分析，以阐明它们与年龄相关的基因表达谱。我们的结果表明，从4个月起，相对于它们在成年期的表达，小胶质细胞和星形胶质细胞中一组与年龄相关的基因表现出一致的上调或下调（称为“衰老” /“衰老”基因） （2个月）。并且大多数成年基因在同一时间点在AD小鼠中表达更高。生物信息学分析表明，小胶质细胞中的衰老基因与炎症反应有关，而星形胶质细胞中的这些基因包括广为人知的AD风险基因，与突触传递或消除有关的基因以及肽酶抑制剂基因。总体而言，我们的RNA序列数据为将来研究小胶质细胞和星形胶质细胞在衰老和淀粉样β诱导的AD病理中的作用提供了宝贵的资源。