Mef2C restrains microglial inflammatory response and is lost in brain ageing in an IFN-I-dependent manner

Aleksandra Deczkowska, Orit Matcovitch-Natan, Afroditi Tsitsou-Kampeli, Sefi Ben-Hamo, Raz Dvir-Szternfeld, Amit Spinrad, Oded Singer, Eyal David, Deborah R. Winter, Lucas K. Smith, Alexander Kertser, Kuti Baruch, Neta Rosenzweig, Anna Terem, Marco Prinz, Saul Villeda, Ami Citri, Ido Amit*, Michal Schwartz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


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.

Original languageEnglish (US)
Article number717
JournalNature communications
Issue number1
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Mef2C restrains microglial inflammatory response and is lost in brain ageing in an IFN-I-dependent manner'. Together they form a unique fingerprint.

Cite this