Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9943446 | The American Journal of Pathology | 2005 | 8 Pages |
Abstract
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by parkinsonism unresponsive to dopaminergic therapy, cerebellar ataxia, and dysautonomia. Neuropathology shows a characteristic neuronal multisystem degeneration that is associated with widespread oligodendroglial α-synuclein (α-SYN) inclusions. Presently no animal model completely replicates the specific neuropathology of MSA. Here we investigated the behavioral and pathological features resulting from oligodendroglial α-SYN overexpression in transgenic mice exposed to mitochondrial inhibition by 3-nitropropionic acid. In transgenic mice 3-nitropropionic acid induced or augmented motor deficits that were associated with MSA-like pathology including striatonigral degeneration and olivopontocerebellar atrophy. Widespread astrogliosis and microglial activation were also observed in the presence of α-SYN in oligodendrocytes. Our results indicate that combined mitochondrial inhibition and overexpression of oligodendroglial α-SYN generates a novel model of MSA that may be useful for evaluating both pathogenesis and treatment strategies.
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Authors
Nadia Stefanova, Markus Reindl, Manuela Neumann, Christian Haass, Werner Poewe, Philipp J. Kahle, Gregor K. Wenning,