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

Wang, Xue Jing ; Ma, Ming Ming ; Zhou, Le Bo ; Jiang, Xiao Yi ; Hao, Miao Miao ; Teng, Robert K.F. ; Wu, Erxi ; Tang, Bei Sha ; Li, Jia Yi LU and Teng, Jun Fang , et al. (2020) In Nature Communications 11(1).
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
11
issue
1
article number
934
publisher
Nature Publishing Group
external identifiers
  • scopus:85079656523
  • pmid:32071315
ISSN
2041-1723
DOI
10.1038/s41467-019-14189-9
language
English
LU publication?
yes
id
156ac471-19c7-44f1-b999-020c62b1dd08
date added to LUP
2020-03-10 11:05:36
date last changed
2024-04-17 04:58:19
@article{156ac471-19c7-44f1-b999-020c62b1dd08,
  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.}},
  author       = {{Wang, Xue Jing and Ma, Ming Ming and Zhou, Le Bo and Jiang, Xiao Yi and Hao, Miao Miao and Teng, Robert K.F. and Wu, Erxi and Tang, Bei Sha and Li, Jia Yi and Teng, Jun Fang and Ding, Xue Bing}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Autonomic ganglionic injection of α-synuclein fibrils as a model of pure autonomic failure α-synucleinopathy}},
  url          = {{http://dx.doi.org/10.1038/s41467-019-14189-9}},
  doi          = {{10.1038/s41467-019-14189-9}},
  volume       = {{11}},
  year         = {{2020}},
}