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大脑中微胶质细胞活动的重新同步与帕金森病运动功能的恢复有关。

Resynchronization of microglial activity in the brain is associated with restoration of motor function in Parkinson's disease.

作者信息

Ye Peizhen, Bi Lei, Qiu Yifan, Yang Min, Liu Yongshan, Hou Yuyi, Zheng Pengcheng, Cao Xiaojuan, Su Jing, Jin Hongjun

机构信息

Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai City, Guangdong Province, 519000, China.

Department of Hematology, Washington University School of Medicine, St. Louis, MO, 63110, USA.

出版信息

Commun Biol. 2025 Aug 9;8(1):1188. doi: 10.1038/s42003-025-08602-x.

Abstract

Neuroinflammation is a key factor in Parkinson's disease (PD) pathogenesis. However, the regional heterogeneity of biomarkers related to inflammation in PD is less well defined. We developed [F]GSK PET imaging to quantify neuroinflammation via the P2X7 receptor (P2X7R) in A53T PD male mice and wild-type (WT) male mice. Montelukast (MK) was administered to mice, and weekly behavior tests confirmed MK's efficacy. [F]L-DOPA/[F]GSK PET, motor testing, autoradiography, and immunofluorescence were performed after MK treatments. MK improved motor function and reduced the brain uptake of [F]GSK, indicating resynchronization of regional microglial activity. The whole brain uptake of [F]GSK was correlated with motor functional restoration, while [F]L-DOPA PET was not. Overall, our study indicated that brain mapping of [F]GSK PET is beneficial for exploring P2X7R-related neuroinflammation, which is correspondent to motor function in PD.

摘要

神经炎症是帕金森病(PD)发病机制中的一个关键因素。然而,与PD炎症相关的生物标志物的区域异质性尚不太明确。我们开发了[F]GSK PET成像技术,以通过P2X7受体(P2X7R)对A53T PD雄性小鼠和野生型(WT)雄性小鼠的神经炎症进行量化。给小鼠施用孟鲁司特(MK),每周进行的行为测试证实了MK的疗效。在MK治疗后进行了[F]左旋多巴/[F]GSK PET、运动测试、放射自显影和免疫荧光检查。MK改善了运动功能并降低了大脑对[F]GSK的摄取,表明区域小胶质细胞活动重新同步。[F]GSK的全脑摄取与运动功能恢复相关,而[F]左旋多巴PET则不然。总体而言,我们的研究表明,[F]GSK PET的脑图谱有助于探索与P2X7R相关的神经炎症,这与PD中的运动功能相对应。

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