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      headline:Mef2C restrains microglial inflammatory response and is lost in brain ageing in an IFN-I-dependent manner
      description:During ageing, microglia acquire a phenotype that may negatively affect brain function. Here we show that ageing microglial phenotype is largely imposed by interferon type I (IFN-I) chronically present in aged brain milieu. Overexpression of IFN-β in the CNS of adult wild-type mice, but not of mice lacking IFN-I receptor on their microglia, induces an ageing-like transcriptional microglial signature, and impairs cognitive performance. Furthermore, we demonstrate that age-related IFN-I milieu downregulates microglial myocyte-specific enhancer factor 2C (Mef2C). Immune challenge in mice lacking Mef2C in microglia results in an exaggerated microglial response and has an adverse effect on mice behaviour. Overall, our data indicate that the chronic presence of IFN-I in the brain microenvironment, which negatively affects cognitive function, is mediated via modulation of microglial activity. These findings may shed new light on other neurological conditions characterized by elevated IFN-I signalling in the brain. Microglia cells in the brain regulate immune responses, but in ageing can negatively affect brain function. Here the authors show that the chronic presence of type I interferon in aged mouse brain impedes cognitive ability by altering microglia transcriptome and limiting Mef2C, a microglia ‘off’ signal.
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         name:Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel
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            address:
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            address:
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            address:
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               type:PostalAddress
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            address:
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      name:Ido Amit
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            name:Weizmann Institute of Science
            address:
               name:Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
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      name:Michal Schwartz
      affiliation:
            name:Weizmann Institute of Science
            address:
               name:Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
      name:Faculty of Biochemistry, Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Anatomy, University of California San Francisco, San Francisco, USA
      name:Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Biological Chemistry, Institute of Life Sciences, Faculty of Natural Sciences, The Hebrew University, Jerusalem, Israel
      name:Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel
      name:Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
      name:BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany
      name:Department of Anatomy, University of California San Francisco, San Francisco, USA
      name:Department of Biological Chemistry, Institute of Life Sciences, Faculty of Natural Sciences, The Hebrew University, Jerusalem, Israel
      name:Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel
      name:Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel

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