Age-related motor dysfunction and neuropathology in a transgenic mouse model of multiple system atrophy

Synapse. 2014 Mar;68(3):98-106. doi: 10.1002/syn.21719. Epub 2013 Nov 15.


Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a progressive degeneration of the striatonigral, olivo-ponto-cerebellar, and autonomic systems. Glial cytoplasmic inclusions (GCIs) containing alpha-synuclein represent the hallmark of MSA and are recapitulated in mice expressing alpha-synuclein in oligodendrocytes. To assess if oligodendroglial expression of human wild-type alpha-synuclein in mice (proteolipid promoter, PLP-SYN) could be associated with age-related deficits, PLP-SYN and wild-type mice were assessed for motor function, brain morphometry, striatal levels of dopamine and metabolites, dopaminergic loss, and distribution of GCIs. PLP-SYN displayed age-related impairments on a beam-traversing task. MRI revealed a significantly smaller brain volume in PLP-SYN mice at 12 months, which further decreased at 18 months together with increased volume of ventricles and cortical atrophy. The distribution of GCIs was reminiscent of MSA with a high burden in the basal ganglia. Mild dopaminergic cell loss was associated with decreased dopamine turnover at 18 months. These data indicate that PLP-SYN mice may recapitulate some of the progressive features of MSA and deliver endpoints for the evaluation of therapeutic strategies.

Keywords: alpha-synuclein; magnetic resonance imaging; motor behavior; multiple system atrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Atrophy
  • Brain / metabolism*
  • Brain / pathology*
  • Cell Death
  • Cerebral Ventricles / pathology
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Dopamine / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Activity
  • Movement Disorders / complications
  • Movement Disorders / metabolism*
  • Movement Disorders / pathology*
  • Multiple System Atrophy / complications
  • Multiple System Atrophy / metabolism*
  • Multiple System Atrophy / pathology*
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Organ Size
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism


  • alpha-Synuclein
  • Dopamine