title: Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  Microglia priming induces a highly conserved transcriptional signature with aging- and disease-specific aspects.
authors.affiliation: Department of Neuroscience, section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. irholtman@gmail.com.
authors.forename: Inge R
authors.initials: IR
authors.lastname: Holtman
authors.affiliation: Department of Neuroscience, section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. divyaraj18@gmail.com.
authors.forename: Divya D
authors.initials: DD
authors.lastname: Raj
authors.affiliation: Allen Institute for Brain Science, Seattle, USA. jeremyinla@gmail.com.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Miller
authors.affiliation: Department of Neuroscience, section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. wandertschaafsma@gmail.com.
authors.forename: Wandert
authors.initials: W
authors.lastname: Schaafsma
authors.affiliation: Department of Neuroscience, section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. zhuoranyin@163.com.
authors.forename: Zhuoran
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Neuroscience, section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. nieske.brouwer@umcg.nl.
authors.forename: Nieske
authors.initials: N
authors.lastname: Brouwer
authors.affiliation: Lundbeck Research USA, Paramus, New Jersey, USA. WES@lundbeck.com.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Wes
authors.affiliation: Lundbeck Research USA, Paramus, New Jersey, USA. TMOE@lundbeck.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Möller
authors.affiliation: Department of Astrocyte Biology and Neurodegeneration, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands. marie.orre@gmail.com.
authors.forename: Marie
authors.initials: M
authors.lastname: Orre
authors.affiliation: Department of Astrocyte Biology and Neurodegeneration, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands. w.kamphuis@nin.knaw.nl.
authors.forename: Willem
authors.initials: W
authors.lastname: Kamphuis
authors.affiliation: Department of Astrocyte Biology and Neurodegeneration, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands. e.hol@nin.knaw.nl.|Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. e.hol@nin.knaw.nl.|Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands. e.hol@nin.knaw.nl.
authors.forename: Elly M
authors.initials: EM
authors.lastname: Hol
authors.affiliation: Department of Neuroscience, section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. h.w.g.m.boddeke@umcg.nl.
authors.forename: Erik W G M
authors.initials: EW
authors.lastname: Boddeke
authors.affiliation: Department of Neuroscience, section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. b.j.l.eggen@umcg.nl.
authors.forename: Bart J L
authors.initials: BJ
authors.lastname: Eggen
mesh_terms: D000375:Aging / Q000235:genetics* / Q000276:immunology; D000544:Alzheimer Disease / Q000235:genetics; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D051379:Mice; D017628:Microglia / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D016328:NF-kappa B