Dual Roles of Microglia in the Basal Ganglia in Parkinson's Disease.
Dual Roles of Microglia in the Basal Ganglia in Parkinson's Disease.
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DOI：
10.3390/ijms22083907
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发表时间：
2021-04-09
影响因子：
5.6
通讯作者：
Tanaka J
中科院分区：
文献类型：
--
作者：
Choudhury ME;Kigami Y;Tanaka J
随着人口年龄的增长，帕金森病（PD）的发病率呈指数级增长。开发新的治疗干预措施需要了解衰老脑细胞在PD发病机制中的参与。在这篇综述中，我们强调了小胶质细胞在PD的病理生理过程中发挥的作用。在PD中，黑质丘脑部（SNc）中的多巴胺能（DA能）神经元变性激活小胶质细胞，然后通过释放潜在的神经毒性因子（包括一氧化氮、细胞因子和活性氧）促进DA能神经元变性。另一方面，小胶质细胞也在基底神经节输出（黑质网状部和苍白球）中被激活，以响应过度活跃的底丘脑核衍生突触释放的过量谷氨酸。然后，激活的小胶质细胞消除了过度活跃的突触。突触消除可能是补偿的潜在机制，尽管DA能神经元大量丢失，但该机制掩盖了PD症状的出现。小胶质细胞的衰老可能与它们在SNc中的神经毒性增强和基底神经节输出中的代偿作用减少有关。小胶质细胞在不同基底神经节区域中的双重作用使得难以开发针对小胶质细胞用于PD治疗的干预措施。
With the increasing age of the population, the incidence of Parkinson’s disease (PD) has increased exponentially. The development of novel therapeutic interventions requires an understanding of the involvement of senescent brain cells in the pathogenesis of PD. In this review, we highlight the roles played by microglia in the basal ganglia in the pathophysiological processes of PD. In PD, dopaminergic (DAergic) neuronal degeneration in the substantia nigra pars compacta (SNc) activates the microglia, which then promote DAergic neuronal degeneration by releasing potentially neurotoxic factors, including nitric oxide, cytokines, and reactive oxygen species. On the other hand, microglia are also activated in the basal ganglia outputs (the substantia nigra pars reticulata and the globus pallidus) in response to excess glutamate released from hyperactive subthalamic nuclei-derived synapses. The activated microglia then eliminate the hyperactive glutamatergic synapses. Synapse elimination may be the mechanism underlying the compensation that masks the appearance of PD symptoms despite substantial DAergic neuronal loss. Microglial senescence may correlate with their enhanced neurotoxicity in the SNc and the reduced compensatory actions in the basal ganglia outputs. The dual roles of microglia in different basal ganglia regions make it difficult to develop interventions targeting microglia for PD treatment.
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通讯作者：
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