title: Isolation of glia from Alzheimer's mice reveals inflammation and dysfunction.
abstract: Reactive astrocytes and microglia are associated with amyloid plaques in Alzheimer's disease (AD). Yet, not much is known about the molecular alterations underlying this reactive phenotype. To get an insight into the molecular changes underlying AD induced astrocyte and microglia reactivity, we performed a transcriptional analysis on acutely isolated astrocytes and microglia from the cortex of aged controls and APPswe/PS1dE9 AD mice. As expected, both cell types acquired a proinflammatory phenotype, which confirms the validity of our approach. Interestingly, we observed that the immune alteration in astrocytes was relatively more pronounced than in microglia. Concurrently, our data reveal that astrocytes display a reduced expression of neuronal support genes and genes involved in neuronal communication. The microglia showed a reduced expression of phagocytosis and/or endocytosis genes. Co-expression analysis of a human AD expression data set and the astrocyte and microglia data sets revealed that the inflammatory changes in astrocytes were remarkably comparable in mouse and human AD, whereas the microglia changes showed less similarity. Based on these findings we argue that chronically proinflammatory astrocyte and microglia phenotypes, showing a reduction of genes involved in neuronal support and neuronal signaling, are likely to contribute to the neuronal dysfunction and cognitive decline in AD.
authors.affiliation: Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands.
authors.forename: Marie
authors.initials: M
authors.lastname: Orre
authors.affiliation: Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: Kamphuis
authors.affiliation: Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands; Cellular and Systems Neurobiology, Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Lana M
authors.initials: LM
authors.lastname: Osborn
authors.affiliation: Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands.
authors.forename: Anne H P
authors.initials: AHP
authors.lastname: Jansen
authors.affiliation: Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands.
authors.forename: Lieneke
authors.initials: L
authors.lastname: Kooijman
authors.affiliation: Neuroregeneration group, Netherlands Institute for Neuroscience (NIN), Amsterdam, the Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: Bossers
authors.affiliation: Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands; Cellular and Systems Neurobiology, Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, the Netherlands; Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: E.M.Hol-2@umcutrecht.nl.
authors.forename: Elly M
authors.initials: EM
authors.lastname: Hol
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology* / Q000523:psychology; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000473:pathology; D003071:Cognition; D004195:Disease Models, Animal; D004705:Endocytosis / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D010587:Phagocytosis / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics
keywords: Alzheimer's disease; Amyloid-β; Astrocytes; Gene expression; Microarray; Microglia; Reactive glia