[HTML][HTML] Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis
Acta neuropathologica communications, 2015•Springer
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 …
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 …
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.
Springer