Ye Peizhen, Bi Lei, Qiu Yifan, Yang Min, Liu Yongshan, Hou Yuyi, Zheng Pengcheng, Cao Xiaojuan, Su Jing, Jin Hongjun
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.
Commun Biol. 2025 Aug 9;8(1):1188. doi: 10.1038/s42003-025-08602-x.
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.
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。