Age-related motor dysfunction and neuropathology in a transgenic mouse model of multiple system atrophy
Article first published online: 15 NOV 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 68, Issue 3, pages 98–106, March 2014
How to Cite
Fernagut, P.O., Meissner, W.G., Biran, M., Fantin, M., Bassil, F., Franconi, J.M. and Tison, F. (2014), Age-related motor dysfunction and neuropathology in a transgenic mouse model of multiple system atrophy. Synapse, 68: 98–106. doi: 10.1002/syn.21719
- Issue published online: 21 JAN 2014
- Article first published online: 15 NOV 2013
- Accepted manuscript online: 31 OCT 2013 02:46AM EST
- Manuscript Accepted: 24 SEP 2013
- Manuscript Received: 10 JUN 2013
- ARAMISE (French Association for Research on Multiple System Atrophy)
- multiple system atrophy;
- magnetic resonance imaging;
- motor behavior
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. Synapse 68:98–106, 2014. © 2013 Wiley Periodicals, Inc.