Autonomic ganglionic injection of α-synuclein fibrils as a model of pure autonomic failure α-synucleinopathy.,Nature Communications

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Autonomic ganglionic injection of α-synuclein fibrils as a model of pure autonomic failure α-synucleinopathy.
Nature Communications ( IF 14.7 ) Pub Date : 2020-02-18 , DOI: 10.1038/s41467-019-14189-9
Xue-Jing Wang _{1,

2} , Ming-Ming Ma ₃ , Le-Bo Zhou _{1,

2} , Xiao-Yi Jiang _{1,

2} , Miao-Miao Hao _{1,

2} , Robert K F Teng ₄ , Erxi Wu ₅ , Bei-Sha Tang _{6,

7} , Jia-Yi Li _{8,

9} , Jun-Fang Teng _{1,

2} , Xue-Bing Ding _{1,

2,

7}

Affiliation

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
Institute of Parkinson and Movement Disorder, Zhengzhou University, Zhengzhou, Henan, 450052, China.
Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China.
Collage of Electronic and Information Engineering, Shenzhen University, Shen Zhen, Guangdong, 518060, China.
Neuroscience Institute and Department of Neurosurgery, Baylor Scott & White Health, Temple, Texas, 76508, USA.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, 410008, China.
Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, 410008, China.
Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A10, 221 84, Lund, Sweden.
Institute of Health Sciences, China Medical University, 110112, Shenyang, China.

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.

中文翻译：

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。

α-突触核蛋白病的特征是自主神经功能障碍和运动障碍。在纯自主神经衰竭（PAF）中，α-突触核蛋白（α-Syn）病理仅限于自主神经系统内，没有运动特征，但缺乏重现 PAF 且无运动功能障碍的小鼠模型。在这里，我们表明，在 TgM83+/- 小鼠中，将 α-Syn 预制原纤维 (PFF) 接种到星状神经节和腹腔神经节中，仅通过自主神经途径向中枢神经系统 (CNS) 和腹腔神经节诱导 α-Syn 病理学的传播。周围器官的双向自主神经支配。与此同时，小鼠出现自主神经功能障碍，表现为直立性低血压、便秘、少汗和嗅觉减退，但没有运动功能障碍。因此，我们建立了由 α-Syn 病理学引起的纯自主神经功能障碍的小鼠模型。该模型可能有助于定义病理性 α-Syn 的传播与 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。

更新日期：2020-02-18

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