Acute microglia ablation induces neurodegeneration in the somatosensory system

被引：61

作者：

Rubino, Stephen J. ^{[1
]}

Mayo, Lior ^{[1
,4
,5
]}

Wimmer, Isabella ^{[2
]}

Siedler, Victoria ^{[2
]}

Brunner, Florian ^{[2
]}

Hametner, Simon ^{[2
]}

Madi, Asaf ^{[3
,6
]}

Lanser, Amanda ^{[1
]}

Moreira, Thais ^{[1
]}

Donnelly, Dustin ^{[1
]}

Cox, Laura ^{[1
]}

Rezende, Rafael Machado ^{[1
]}

Butovsky, Oleg ^{[1
,3
]}

Lassmann, Hans ^{[2
]}

Weiner, Howard L. ^{[1
,3
]}

机构：

[1] Harvard Med Sch, Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA

[2] Med Univ Vienna, Dept Neuroimmunol, Spitalgasse 4, A-1090 Vienna, Austria

[3] Harvard Med Sch, Brigham & Womens Hosp, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA

[4] Tel Aviv Univ, Sch Mol Cell Biol & Biotechnol, George S Wise Fac Life Sci, IL-69978 Tel Aviv, Israel

[5] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel

[6] Tel Aviv Univ, Sackler Sch Med, Dept Pathol, IL-69978 Tel Aviv, Israel

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

奥地利科学基金会;

关键词：

AICARDI-GOUTIERES SYNDROME; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; SYNAPSE FORMATION; GENE-EXPRESSION; INTERFERON-BETA; MYELOID CELLS; MONOCYTES; SIGNATURE; MOUSE;

D O I：

10.1038/s41467-018-05929-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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