Transcriptomic profiling of microglia and astrocytes throughout aging

J Neuroinflammation. 2020 Apr 1;17(1):97. doi: 10.1186/s12974-020-01774-9.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Aging; Alzheimer’s disease (AD); Astrocyte; Microglia; RNA-seq.

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Astrocytes / metabolism*
  • Brain / metabolism*
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression Profiling
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism*
  • Presenilin-1 / genetics
  • Transcriptome*

Substances

  • Amyloid beta-Protein Precursor
  • Presenilin-1