Details

Autor(en) / Beteiligte

• Fernagut, P.O.
• Meissner, W.G.
• Biran, M.
• Fantin, M.
• Bassil, F.
• Franconi, J.M.
• Tison, F.

Titel

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

Ist Teil von

• Synapse (New York, N.Y.), 2014-03, Vol.68 (3), p.98-106

Ort / Verlag

United States: Blackwell Publishing Ltd

Erscheinungsjahr

2014

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• ABSTRACT 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. This work demonstrates that a genetic mouse model of multiple system atrophy recapitulates some of the progressive features of the disease, including age‐related behavioural impairments and brain atrophy, together with a high burden of alpha‐synuclein accumulation in the basal ganglia. This study delivers endpoints for the evaluation of therapeutic strategies.