Acute microglia ablation induces neurodegeneration in the somatosensory system

Stephen J. Rubino, Lior Mayo, Isabella Wimmer, Victoria Siedler, Florian Brunner, Simon Hametner, Asaf Madi, Amanda Lanser, Thais Moreira, Dustin Donnelly, Laura Cox, Rafael Machado Rezende, Oleg Butovsky, Hans Lassmann, Howard L. Weiner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Previous studies have reported that microglia depletion leads to impairment of synapse formation and these cells rapidly repopulate from CNS progenitors. However, the impact of microglia depletion and repopulation in the long-term state of the CNS environment has not been characterized. Here, we report that acute and synchronous microglia depletion and subsequent repopulation induces gray matter microgliosis, neuronal death in the somatosensory cortex and ataxia-like behavior. We find a type 1 interferon inflammatory signature in degenerating somatosensory cortex from microglia-depleted mice. Transcriptomic and mass cytometry analysis of repopulated microglia demonstrates an interferon regulatory factor 7-driven activation state. Minocycline and anti-IFNAR1 antibody treatment attenuate the CNS type 1 interferon-driven inflammation, restore microglia homeostasis and reduce ataxic behavior. Neither microglia depletion nor repopulation impact neuropathology or T-cell responses during experimental autoimmune encephalomyelitis. Together, we found that acute microglia ablation induces a type 1 interferon activation state of gray matter microglia associated with acute neurodegeneration.

Original languageEnglish
Article number4578
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2018

Funding

FundersFunder number
National Institute on AgingR01AG043975

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