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The neural substrates of rapid-onset Dystonia-Parkinsonism.

ABSTRACT: Although dystonias are a common group of movement disorders, the mechanisms by which brain dysfunction results in dystonia are not understood. Rapid-onset Dystonia-Parkinsonism (RDP) is a hereditary dystonia caused by mutations in the ATP1A3 gene. Affected individuals can be free of symptoms for years, but rapidly develop persistent dystonia and Parkinsonism-like symptoms after a stressful experience. Using a mouse model, we found that an adverse interaction between the cerebellum and basal ganglia can account for the symptoms of these individuals. The primary instigator of dystonia was the cerebellum, whose aberrant activity altered basal ganglia function, which in turn caused dystonia. This adverse interaction between the cerebellum and basal ganglia was mediated through a di-synaptic thalamic pathway that, when severed, alleviated dystonia. Our results provide a unifying hypothesis for the involvement of cerebellum and basal ganglia in the generation of dystonia and suggest therapeutic strategies for the treatment of RDP.

SUBMITTER: Calderon DP

PROVIDER: S-EPMC3430603 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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The neural substrates of rapid-onset Dystonia-Parkinsonism.

Calderon D Paola DP Fremont Rachel R Kraenzlin Franca F Khodakhah Kamran K

Nature neuroscience 20110206 3

Although dystonias are a common group of movement disorders, the mechanisms by which brain dysfunction results in dystonia are not understood. Rapid-onset Dystonia-Parkinsonism (RDP) is a hereditary dystonia caused by mutations in the ATP1A3 gene. Affected individuals can be free of symptoms for years, but rapidly develop persistent dystonia and Parkinsonism-like symptoms after a stressful experience. Using a mouse model, we found that an adverse interaction between the cerebellum and basal gang ...[more]

PMID: 21297628

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Revising rapid-onset dystonia-parkinsonism: Broadening indications for ATP1A3 testing.

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Characterization of Atp1a3 mutant mice as a model of rapid-onset dystonia with parkinsonism.

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New triggers and non-motor findings in a family with rapid-onset dystonia-parkinsonism.

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Project description: Not available

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