Abstract：
The role of alpha-synuclein in Parkinson\'s disease has been heavily investigated since its discovery as a component of Lewy bodies. Recent rodent data demonstrate that alpha-synuclein strain structure is critical for differential propagation and toxicity. Based on these findings, we have compared, for the first time, in this pilot study, the capacity of two alpha-synuclein strains and patient-derived Lewy body extracts to model synucleinopathies after intra-putaminal injection in the non-human primate brain. Functional alterations triggered by these injections were evaluated in vivo using glucose positron emission tomography imaging. Post-mortem immunohistochemical and biochemical analyses were used to detect neuropathological alterations in the dopaminergic system and alpha-synuclein pathology propagation. In vivo results revealed a decrease in glucose metabolism more pronounced in alpha-synuclein strain-injected animals. Histology showed a decreased number of dopaminergic tyrosine hydroxylase-positive cells in the substantia nigra to different extents according to the inoculum used. Biochemistry revealed that alpha-synuclein-induced aggregation, phosphorylation, and propagation in different brain regions are strain-specific. Our findings show that distinct alpha-synuclein strains can induce specific patterns of synucleinopathy in the non-human primate, changes in the nigrostriatal pathway, and functional alterations that resemble early-stage Parkinson\'s disease.
摘要：
自从α-突触核蛋白作为路易体的一个组成部分被发现以来,已经对其在帕金森病中的作用进行了大量研究。最近的啮齿动物数据表明，α-突触核蛋白应变结构对于差异传播和毒性至关重要。基于这些发现,我们比较了，第一次,在这项试点研究中，两种α-突触核蛋白菌株和患者来源的路易体提取物在非人类灵长类动物脑壳内注射后模拟突触核蛋白病的能力。使用葡萄糖正电子发射断层扫描成像在体内评估由这些注射触发的功能改变。死后免疫组织化学和生化分析用于检测多巴胺能系统和α-突触核蛋白病理学传播的神经病理学改变。体内结果显示，在注射α-突触核蛋白菌株的动物中，葡萄糖代谢的降低更为明显。组织学显示，根据所使用的接种物，黑质中多巴胺能酪氨酸羟化酶阳性细胞的数量有所减少。生物化学显示α-突触核蛋白诱导的聚集，磷酸化,在不同的大脑区域的传播是应变特异性的。我们的发现表明，不同的α-突触核蛋白菌株可以在非人灵长类动物中诱导突触核蛋白病的特定模式，黑质纹状体途径的变化，和类似早期帕金森病的功能改变。
