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

P.O. Fernagut, W.G. Meissner, M. Biran, M. Fantin, F. Bassil, J.M. Franconi, F. Tison
Synapse. 2013-11-15; 68(3): 98-106
DOI: 10.1002/syn.21719

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

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

Fernagut PO(1), Meissner WG, Biran M, Fantin M, Bassil F, Franconi JM, Tison F.

Author information:
(1)Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293,
F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR
5293, F-33000 Bordeaux, France.

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.

Copyright © 2013 Wiley Periodicals, Inc.

DOI: 10.1002/syn.21719
PMID: 24243499 [Indexed for MEDLINE]

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