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

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.

Ma, Ming MingFirst Affiliated Hospital of Zhengzhou University (författare)
Zhou, Le BoFirst Affiliated Hospital of Zhengzhou University (författare)
Jiang, Xiao YiFirst Affiliated Hospital of Zhengzhou University (författare)
Hao, Miao MiaoFirst Affiliated Hospital of Zhengzhou University (författare)
Teng, Robert K.F.Shenzhen University (författare)
Wu, ErxiBaylor University Medical Centre (författare)
Tang, Bei ShaCentral South University, China (författare)
Li, Jia YiLund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,China Medical University, Shenyang(Swepub:lu)mphy-jli (författare)
Teng, Jun FangFirst Affiliated Hospital of Zhengzhou University (författare)
Ding, Xue BingFirst Affiliated Hospital of Zhengzhou University,Central South University, China (författare)
First Affiliated Hospital of Zhengzhou UniversityShenzhen University (creator_code:org_t)

Ingår i:Nature Communications: Springer Science and Business Media LLC11:12041-1723

Av författaren/redakt...: Wang, Xue Jing; Ma, Ming Ming; Zhou, Le Bo; Jiang, Xiao Yi; Hao, Miao Miao; Teng, Robert K.F ...; visa fler...; Wu, Erxi; Tang, Bei Sha; Li, Jia Yi; Teng, Jun Fang; Ding, Xue Bing; visa färre...

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