当前位置: X-MOL 学术Nat. Commun. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Acute microglia ablation induces neurodegeneration in the somatosensory system.
Nature Communications ( IF 14.7 ) Pub Date : 2018-11-01 , DOI: 10.1038/s41467-018-05929-4
Stephen J Rubino 1 , Lior Mayo 1, 2 , Isabella Wimmer 3 , Victoria Siedler 3 , Florian Brunner 3 , Simon Hametner 3 , Asaf Madi 4, 5 , Amanda Lanser 1 , Thais Moreira 1 , Dustin Donnelly 1 , Laura Cox 1 , Rafael Machado Rezende 1 , Oleg Butovsky 1, 4 , Hans Lassmann 3 , Howard L Weiner 1, 4
Affiliation  

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.

中文翻译:

急性小胶质细胞消融诱导体感系统的神经变性。

以前的研究报告说,小胶质细胞耗竭会导致突触形成受损,并且这些细胞会迅速从 CNS 祖细胞中重新增殖。然而,在中枢神经系统环境的长期状态下,小胶质细胞耗竭和再增殖的影响尚未得到表征。在这里,我们报告急性和同步小胶质细胞耗竭和随后的再增殖诱导灰质小胶质细胞增生、体感皮层神经元死亡和共济失调样行为。我们在小胶质细胞耗竭小鼠的退化体感皮层中发现了 1 型干扰素炎症特征。重新填充的小胶质细胞的转录组学和质谱分析表明干扰素调节因子 7 驱动的激活状态。米诺环素和抗 IFNAR1 抗体治疗可减轻 CNS 1 型干扰素驱动的炎症,恢复小胶质细胞稳态并减少共济失调行为。在实验性自身免疫性脑脊髓炎期间,小胶质细胞耗竭和再增殖都不会影响神经病理学或 T 细胞反应。总之,我们发现急性小胶质细胞消融诱导了与急性神经变性相关的灰质小胶质细胞的 1 型干扰素激活状态。
更新日期:2018-11-02
down
wechat
bug