Depletion of microglia augments the dopaminergic neurotoxicity of MPTP.
Depletion of microglia augments the dopaminergic neurotoxicity of MPTP.
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小胶质细胞的消耗增强了 MPTP 的多巴胺能神经毒性。
DOI：
10.1096/fj.201700833rr
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Yang X;Ren H;Wood K;Li M;Qiu S;Shi FD;Ma C;Liu Q
小胶质细胞的激活及其产生的各种物质已被认为与帕金森病(PD)的病理发展有关，但小胶质细胞在PD中的确切作用仍有待确定。小胶质细胞的存活依赖于集落刺激因子1受体(CSF1R)信号，抑制CSF1R可以迅速消除中枢神经系统中的小胶质细胞。在1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)诱导的小鼠帕金森病模型上，CSF1R抑制剂PLX3397耗尽小胶质细胞，加重了运动功能的损害和多巴胺能神经元的丢失。此外，MPTP暴露后，小胶质细胞的枯竭增加了炎性介质的产生，并增加了脑组织中白细胞的渗透。小胶质细胞耗竭导致的MPTP神经毒性在淋巴细胞缺陷小鼠中也被观察到。此外，小胶质细胞的枯竭不影响脑源性神经营养因子的产生，但它显著增加了MPTP处理后星形胶质细胞产生的炎性介质。我们的研究结果表明，小胶质细胞对MPTP诱导的神经炎症和多巴胺能神经毒性具有保护作用。-Yang，X.，Ren，H.，Wood，K.，Li，M.，Chu，S.，Shii，F.D.，Ma，C.，Liu，Q。小胶质细胞的耗竭增加了MPTP的多巴胺能神经毒性。
The activation of microglia and the various substances they produce have been linked to the pathologic development of Parkinson’s disease (PD), but the precise role of microglia in PD remains to be defined. The survival of microglia depends on colony-stimulating factor 1 receptor (CSF1R) signaling, and CSF1R inhibition results in rapid elimination of microglia in the central nervous system. Using a mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment, we showed that the depletion of microglia via the CSF1R inhibitor PLX3397 exacerbated the impairment of locomotor activities and the loss of dopaminergic neurons. Further, depletion of microglia augmented the production of inflammatory mediators and infiltration of leukocytes in the brain after MPTP exposure. Microglia depletion–induced aggravation of MPTP neurotoxicity was also seen in lymphocyte-deficient mice. In addition, the depletion of microglia did not affect the production of brain-derived neurotrophic factor, but it dramatically augmented the production of inflammatory mediators by astrocytes after MPTP treatment. Our findings suggest microglia play a protective role against MPTP-induced neuroinflammation and dopaminergic neurotoxicity.—Yang, X., Ren, H., Wood, K., Li, M., Qiu, S., Shi, F.-D., Ma, C., Liu, Q. Depletion of microglia augments the dopaminergic neurotoxicity of MPTP.