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Acute microglia ablation induces neurodegeneration in the somatosensory system

Author

Listed:
  • Stephen J. Rubino

    (Harvard Medical School)

  • Lior Mayo

    (Harvard Medical School
    Tel-Aviv University)

  • 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
    Tel Aviv University)

  • 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
    Harvard Medical School)

  • Hans Lassmann

    (Medical University of Vienna)

  • Howard L. Weiner

    (Harvard Medical School
    Harvard Medical School)

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.

Suggested Citation

  • 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, 2018. "Acute microglia ablation induces neurodegeneration in the somatosensory system," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05929-4
    DOI: 10.1038/s41467-018-05929-4
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    Cited by:

    1. Jiyun Peng & Qian Zou & Min-Jie Chen & Chao-Lin Ma & Bao-Ming Li, 2022. "Motor deficits seen in microglial ablation mice could be due to non-specific damage from high dose diphtheria toxin treatment," Nature Communications, Nature, vol. 13(1), pages 1-4, December.

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