Animal models of multiple system atrophy.

P.-O. Fernagut, F. Tison
Neuroscience. 2012-06-01; 211: 77-82
DOI: 10.1016/j.neuroscience.2011.09.044

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https://www.bordeaux-neurocampus.fr/12623

Fernagut PO(1), Tison F.

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

Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative
disorder clinically characterized by a variable combination of dysautonomia,
levodopa-unresponsive parkinsonian and cerebellar symptoms. Neurodegeneration in
MSA occurs in the substantia nigra, putamen, inferior olive, pontine and
brainstem nuclei, as well as intermediolateral cell column of the spinal cord.
MSA is recognized as a synucleinopathy due to the accumulation of insoluble
alpha-synuclein in oligodendroglial cytoplasmic inclusions. Several animal
models have been developed in order to reproduce various clinical and
pathological features of MSA. Using « double toxin-double lesion » or « single
toxin-double lesion », neurotoxin-based models were designed in rats, mice and
non-human primates to reproduce the neuropathology of MSA in the nigrostriatal
system while gene-based models were developed in mice to reproduce the
accumulation of insoluble alpha-synuclein in oligodendrocytes. Both approaches
have then been merged to create optimized, dual-hit models. This review
describes the different animal models of MSA, their respective advantages and
limitations and their usefulness to decipher the pathophysiology of MSA then to
define efficient symptomatic and disease-modifying therapies. This article is
part of a Special Issue entitled: Neuroscience Disease Models.