Autonomic ganglionic injection of α-synuclein fibrils as a model of pure autonomic failure α-synucleinopathy

Xue-Jing Wang (), Ming-Ming Ma, Le-Bo Zhou, Xiao-Yi Jiang, Miao-Miao Hao, Robert K. F. Teng, Erxi Wu, Bei-Sha Tang (), Jia-Yi Li (), Jun-Fang Teng () and Xue-Bing Ding ()
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Xue-Jing Wang: The First Affiliated Hospital of Zhengzhou University
Ming-Ming Ma: Affiliated People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital
Le-Bo Zhou: The First Affiliated Hospital of Zhengzhou University
Xiao-Yi Jiang: The First Affiliated Hospital of Zhengzhou University
Miao-Miao Hao: The First Affiliated Hospital of Zhengzhou University
Robert K. F. Teng: Shenzhen University
Erxi Wu: Baylor Scott & White Health
Bei-Sha Tang: Xiangya Hospital
Jia-Yi Li: Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University
Jun-Fang Teng: The First Affiliated Hospital of Zhengzhou University
Xue-Bing Ding: The First Affiliated Hospital of Zhengzhou University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-019-14189-9

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