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Models of Multiple System Atrophy

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Behavioral Neurobiology of Huntington's Disease and Parkinson's Disease

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 22))

Abstract

Multiple system atrophy (MSA) is a predominantly sporadic, adult-onset, fatal neurodegenerative disease of unknown etiology. MSA is characterized by autonomic failure, levodopa-unresponsive parkinsonism, cerebellar ataxia and pyramidal signs in any combination. MSA belongs to a group of neurodegenerative disorders termed α-synucleinopathies, which also include Parkinson’s disease and dementia with Lewy bodies. Their common pathological feature is the occurrence of abnormal α-synuclein positive inclusions in neurons or glial cells. In MSA, the main cell type presenting aggregates composed of α-synuclein are oligodendroglial cells . This pathological hallmark, also called glial cytoplasmic inclusions (GCIs) , is associated with progressive and profound neuronal loss in various regions of the brain. The development of animal models of MSA is justified by the limited understanding of the mechanisms of neurodegeneration and GCIs formation, which is paralleled by a lack of therapeutic strategies. Two main types of rodent models have been generated to replicate different features of MSA neuropathology. On one hand, neurotoxin-based models have been produced to reproduce neuronal loss in substantia nigra pars compacta and striatum. On the other hand, transgenic mouse models with overexpression of α-synuclein in oligodendroglia have been used to reproduce GCIs-related pathology. This chapter gives an overview of the atypical Parkinson’s syndrome MSA and summarizes the currently available MSA animal models and their relevance for pre-clinical testing of disease-modifying therapies.

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Acknowledgments

This work was supported by grants of the Austrian Science Fund (FWF) P25161 and F4404.

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  1. Division of Neurobiology, Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria

    Lisa Fellner, Gregor K. Wenning & Nadia Stefanova

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  1. Lisa Fellner
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  2. Gregor K. Wenning
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  3. Nadia Stefanova
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Correspondence to Lisa Fellner .

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  1. Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tübingen, Germany

    Hoa Huu Phuc Nguyen

  2. Dept of Experimental Medical Science, Lund University, Lund, Sweden

    M. Angela Cenci

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Fellner, L., Wenning, G.K., Stefanova, N. (2013). Models of Multiple System Atrophy. In: Nguyen, H., Cenci, M. (eds) Behavioral Neurobiology of Huntington's Disease and Parkinson's Disease. Current Topics in Behavioral Neurosciences, vol 22. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2013_269

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