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

Research output: Contribution to journalArticle

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.

Details

Authors
  • 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
  • Xue Bing Ding
Organisations
External organisations
  • First Affiliated Hospital of Zhengzhou University
  • Baylor University Medical Centre
  • Central South University, China
  • China Medical University, Shenyang
  • Shenzhen University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
Original languageEnglish
Article number934
JournalNature Communications
Volume11
Issue number1
Publication statusPublished - 2020
Publication categoryResearch
Peer-reviewedYes