Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis

Inge R. Holtman, Divya D. Raj, Jeremy A. Miller, Wandert Schaafsma, Zhuoran Yin, Nieske Brouwer, Paul D. Wes, Thomas Möller, Marie Orre, Willem Kamphuis, Elly M. Hol, Erik W.G.M. Boddeke, Bart J.L. Eggen

Research output: Contribution to journalArticlepeer-review

342 Scopus citations

Abstract

INTRODUCTION: Microglia are tissue macrophages of the central nervous system that monitor brain homeostasis and react upon neuronal damage and stress. Aging and neurodegeneration induce a hypersensitive, pro-inflammatory phenotype, referred to as primed microglia. To determine the gene expression signature of priming, the transcriptomes of microglia in aging, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) mouse models were compared using Weighted Gene Co-expression Network Analysis (WGCNA).

RESULTS: A highly consistent consensus transcriptional profile of up-regulated genes was identified, which prominently differed from the acute inflammatory gene network induced by lipopolysaccharide (LPS). Where the acute inflammatory network was significantly enriched for NF-κB signaling, the primed microglia profile contained key features related to phagosome, lysosome, antigen presentation, and AD signaling. In addition, specific signatures for aging, AD, and ALS were identified.

CONCLUSION: Microglia priming induces a highly conserved transcriptional signature with aging- and disease-specific aspects.

Original languageEnglish (US)
Pages (from-to)31
Number of pages1
JournalActa Neuropathologica Communications
Volume3
DOIs
StatePublished - May 23 2015
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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