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 and Howard L. Weiner ()
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Stephen J. Rubino: Harvard Medical School
Lior Mayo: Harvard Medical School
Isabella Wimmer: Medical University of Vienna
Victoria Siedler: Medical University of Vienna
Florian Brunner: Medical University of Vienna
Simon Hametner: Medical University of Vienna
Asaf Madi: Harvard Medical School
Amanda Lanser: Harvard Medical School
Thais Moreira: Harvard Medical School
Dustin Donnelly: Harvard Medical School
Laura Cox: Harvard Medical School
Rafael Machado Rezende: Harvard Medical School
Oleg Butovsky: Harvard Medical School
Hans Lassmann: Medical University of Vienna
Howard L. Weiner: Harvard Medical School

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05929-4

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