The motor and nonmotor symptoms of PD involve several brain regions. However, whether α-syn pathology originating from the SNc can directly lead to the pathological changes in distant cerebral regions and induce PD-related symptoms remains unclear. Here, AAV9-synapsin-mCherry-human SNCA (A53T) was injected into the unilateral SNc of mice. Motor function and olfactory sensitivity were evaluated. Our results showed that AAV9-synapsin-mCherry-human SNCA was continuously expressed in SNc. The animals showed mild motor and olfactory dysfunction at 7 months after viral injection. The pathology in SNc was characterized by the loss of dopaminergic neurons accompanied by ER stress. In the striatum, hα-syn expression was high, CaMKβ-2 and NR2B expression decreased, and active synapses reduced. In the olfactory bulb, hα-syn expression was high, and aging cells in the mitral layer increased. The results suggested that hα-syn was transported in the striatum and OB along the nerve fibers that originated from the SNc and induced pathological changes in the distant cerebral regions, which contributed to the motor and nonmotor symptoms of PD.

中文翻译：

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hα-syn（A53T）在帕金森氏病发病机理中的非典型作用：突触病理学和神经元衰老。

PD的运动和非运动症状涉及多个大脑区域。然而，尚不清楚源自SNc的α- syn病理是否可以直接导致远处大脑区域的病理变化并诱发PD相关症状。在此，将AAV9-突触核蛋白-mCherry-人SNCA（A53T）注射到小鼠的单侧SNc中。评估运动功能和嗅觉敏感性。我们的结果表明，AAV9-突触核蛋白-mCherry-人SNCA在SNc中持续表达。病毒注射后7个月，这些动物表现出轻度运动和嗅觉功能障碍。SNc的病理特征是多巴胺能神经元丢失并伴有ER应激。在纹状体中，h α -syn表达是高的，钙调蛋白激酶β-2和NR2B表达减少，而主动突触减少。在嗅球，H α -syn表达是高的，并在二尖瓣层老化细胞增加。结果表明使得h α -syn在纹状体和OB沿着神经纤维源自黑质致密部和诱导在遥远的脑区的病理变化，这有助于电机和非运动PD症状被运输。