Striatal-Inoculation of α-Synuclein Preformed Fibrils Aggravated the Phenotypes of REM Sleep without Atonia in A53T BAC-SNCA Transgenic Mice

Int J Mol Sci. 2022 Nov 2;23(21):13390. doi: 10.3390/ijms232113390.

Abstract

Accumulation of α-synuclein (α-syn) is the pathological hallmark of α-synucleinopathy. Rapid eye movement (REM) sleep behavior disorder (RBD) is a pivotal manifestation of α-synucleinopathy including Parkinson's disease (PD). RBD is clinically confirmed by REM sleep without atonia (RWA) in polysomnography. To accurately characterize RWA preceding RBD and their underlying α-syn pathology, we inoculated α-syn preformed fibrils (PFFs) into the striatum of A53T human α-syn BAC transgenic (A53T BAC-SNCA Tg) mice which exhibit RBD-like phenotypes with RWA. RWA phenotypes were aggravated by PFFs-inoculation in A53T BAC-SNCA Tg mice at 1 month after inoculation, in which prominent α-syn pathology in the pedunculopontine nucleus (PPN) was observed. The intensity of RWA phenotype could be dependent on the severity of the underlying α-syn pathology.

Keywords: Parkinson’s disease; RBD; REM sleep; REM sleep without atonia; α-synuclein.

MeSH terms

  • Animals
  • Humans
  • Mice
  • Mice, Transgenic
  • Muscle Hypotonia
  • Phenotype
  • REM Sleep Behavior Disorder* / genetics
  • Sleep, REM
  • Synucleinopathies* / genetics
  • alpha-Synuclein / genetics

Substances

  • alpha-Synuclein
  • SNCA protein, human
  • Snca protein, mouse