Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-00769-0
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Funding
- Advanced European Research Council grants [232835]
- EU Seventh Framework Program HEALTH [279017]
- Israel Science Foundation (ISF)-research grant [991/16]
- ISF-Legacy Heritage Biomedical Science Partnership-research grant [1354/15]
- Consolidated Anti-Aging Foundation (CAFF)
- European Research Council [309788]
- Israeli Science Foundation [1782/11]
- BLUEPRINT FP7 consortium
- Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine
- Minerva Stiftung research grant
- Israeli Ministry of Science, Technology and Space
- David and Fela Shapell Family Foundation
- National Human Genome Research Institute Center for Excellence in Genome Science [1P50HG006193]
- BMBF
- Sobek-Stiftung
- DFG [SFB 992, SFB1140]
- ERA-Net NEURON initiative NEURO-IFN
- Sonderlinie Hochschulmedizin, project neuroinflammation in neurodegeneration
- [SFB/TRR167]
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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-beta 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.
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