评估 CSF-1R 抑制在帕金森病动物模型中对小胶质细胞耗竭的神经保护作用。
Evaluation of the Neuroprotective Effect of Microglial Depletion by CSF-1R Inhibition in a Parkinson's Animal Model.
机构信息
Division of Applied RI, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 01812, South Korea.
Radiological and Medico-Oncological Sciences, University of Science and Technology, Daejeon, South Korea.
出版信息
Mol Imaging Biol. 2020 Aug;22(4):1031-1042. doi: 10.1007/s11307-020-01485-w.
PURPOSE
Neuroinflammation in Parkinson's disease (PD) is known to play a pivotal role in progression to neuronal degeneration. It has been reported that colony-stimulation factor 1 receptor (CSF-1R) inhibition can effectively deplete microglia. However, its therapeutic efficacy in PD is unclear still now.
PROCEDURES
To elucidate this issue, we examined the contribution of microglial depletion to PD by behavioral testing, positron emission tomography (PET) imaging, and immunoassays in sham, PD, and microglial depletion PD model (PLX3397 was administered to PD groups, with n = 6 in each group).
RESULTS
The microglial depletion in PD model showed improved sensory motor function and depressive-like behavior. NeuroPET revealed that PLX3397 treatment resulted in partial recovery of striatal neuro-inflammatory functions (binding values of [F]DPA-174 for PD, 1.47 ± 0.12, p < 0.01 vs. for PLX3397 in PD: 1.33 ± 0.26) and the dopaminergic (binding values of F-FP-CIT for PD, 1.32 ± 0.07 vs. for PLX3397 in PD: 1.54 ± 0.10, p < 0.01) and glutamatergic systems (binding values of [F]FPEB for PD: 9.22 ± 0.54 vs. for PLX3397 Tx in PD: 9.83 ± 0.96, p > 0.05). Western blotting for microglia showed similar changes.
CONCLUSION
Microglial depletion has inflammation-related therapeutic effects, which have beneficial effects on motor and nonmotor symptoms of PD.
目的
帕金森病（PD）中的神经炎症被认为在神经元变性进展中起关键作用。据报道，集落刺激因子 1 受体（CSF-1R）抑制可有效耗尽小胶质细胞。然而，其在 PD 中的治疗效果尚不清楚。
过程
为了阐明这个问题，我们通过行为测试、正电子发射断层扫描（PET）成像和免疫测定检查了小胶质细胞耗竭对 PD 的贡献，在假手术、PD 和小胶质细胞耗竭 PD 模型中进行了检查（PLX3397 给予 PD 组，每组 n=6）。
结果
PD 模型中的小胶质细胞耗竭显示出改善的感觉运动功能和抑郁样行为。神经 PET 显示，PLX3397 治疗导致纹状体神经炎症功能部分恢复（[F]DPA-174 的结合值为 PD，1.47±0.12，p<0.01，与 PD 中的 PLX3397 相比：1.33±0.26）和多巴胺能（F-FP-CIT 的结合值为 PD，1.32±0.07，与 PD 中的 PLX3397 相比：1.54±0.10，p<0.01）和谷氨酸能系统（[F]FPEB 的结合值为 PD：9.22±0.54，与 PD 中的 PLX3397 Tx 相比：9.83±0.96，p>0.05）。小胶质细胞的 Western 印迹显示出相似的变化。
结论
小胶质细胞耗竭具有与炎症相关的治疗效果，对 PD 的运动和非运动症状有有益影响。
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