Autonomic ganglionic injection of α-synuclein fibrils as a model of pure autonomic failure α-synucleinopathy
Autonomic ganglionic injection of α-synuclein fibrils as a model of pure autonomic failure α-synucleinopathy
复制标题
自主神经节注射α-突触核蛋白原纤维作为纯自主神经衰竭α-突触核蛋白病的模型
DOI：
10.1038/s41467-019-14189-9
复制
发表时间：
2020
影响因子：
16.6
通讯作者：
Ding XB
中科院分区：
文献类型：
--
作者：
Wang XJ Ma MM Zhou LB Jiang XY Hao MM Teng RKF Wu E Tang BS Li JY Teng JF;Ding XB
α-突触核蛋白病以自主神经功能障碍和运动障碍为特征。在纯自主神经衰竭（PAF）中，α-突触核蛋白（α-Syn）病理局限于自主神经系统内，无运动特征，但缺乏再现PAF而无运动功能障碍的小鼠模型。在TgM83+/−小鼠中，将α-Syn预制原纤维（pff）接种到星状神经节和乳糜泻神经节中，可诱导α-Syn病理仅通过自主神经通路双向传播到中枢神经系统（CNS）和周围器官的自主神经支配。同时，小鼠出现自主神经功能障碍，表现为体位性低血压、便秘、少汗和低血，无运动功能障碍。因此，我们建立了由α-Syn病理引起的纯自主神经功能障碍小鼠模型。该模型可能有助于确定病理性α-Syn的传递与α-突触核蛋白病中自主神经功能障碍的主要特征之间的机制联系。
α-Synucleinopathies are characterized by autonomic dysfunction and motor impairments. In the pure autonomic failure (PAF), α-synuclein (α-Syn) pathology is confined within the autonomic nervous system with no motor features, but mouse models recapitulating PAF without motor dysfunction are lacking. Here, we show that in TgM83+/−mice, inoculation of α-Syn preformed fibrils (PFFs) into the stellate and celiac ganglia induces spreading of α-Syn pathology only through the autonomic pathway to both the central nervous system (CNS) and the autonomic innervation of peripheral organs bidirectionally. In parallel, the mice develop autonomic dysfunction, featured by orthostatic hypotension, constipation, hypohidrosis and hyposmia, without motor dysfunction. Thus, we have generated a mouse model of pure autonomic dysfunction caused by α-Syn pathology. This model may help define the mechanistic link between transmission of pathological α-Syn and the cardinal features of autonomic dysfunction in α-synucleinopathy.