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The neural substrates of Rapid-Onset Dystonia-Parkinsonism

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 is a hereditary dystonia caused by mutations in the ATP1A3 gene. Affected subjects can be symptom free for years but rapidly...

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Autores principales: Calderon, D. Paola, Fremont, Rachel, Kraenzlin, Franca, Khodakhah, Kamran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430603/
https://www.ncbi.nlm.nih.gov/pubmed/21297628
http://dx.doi.org/10.1038/nn.2753
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author Calderon, D. Paola
Fremont, Rachel
Kraenzlin, Franca
Khodakhah, Kamran
author_facet Calderon, D. Paola
Fremont, Rachel
Kraenzlin, Franca
Khodakhah, Kamran
author_sort Calderon, D. Paola
collection PubMed
description 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 is a hereditary dystonia caused by mutations in the ATP1A3 gene. Affected subjects can be symptom free for years but rapidly develop persistent dystonia and parkinsonism-like symptoms after a stressful experience. Using a mouse model here we show that an adverse interaction between the cerebellum and basal ganglia can account for the symptoms of the patients. The primary instigator of dystonia is the cerebellum whose aberrant activity alters basal ganglia function which in turn causes dystonia. This adverse interaction between the cerebellum and basal ganglia is mediated through a di-synaptic thalamic pathway which when severed is effective in alleviating dystonia. Our results provide a unifying hypothesis for the involvement of cerebellum and basal ganglia in generation of dystonia and suggest therapeutic strategies for the treatment of RDP.
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spelling pubmed-34306032012-08-29 The neural substrates of Rapid-Onset Dystonia-Parkinsonism Calderon, D. Paola Fremont, Rachel Kraenzlin, Franca Khodakhah, Kamran Nat Neurosci Article 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 is a hereditary dystonia caused by mutations in the ATP1A3 gene. Affected subjects can be symptom free for years but rapidly develop persistent dystonia and parkinsonism-like symptoms after a stressful experience. Using a mouse model here we show that an adverse interaction between the cerebellum and basal ganglia can account for the symptoms of the patients. The primary instigator of dystonia is the cerebellum whose aberrant activity alters basal ganglia function which in turn causes dystonia. This adverse interaction between the cerebellum and basal ganglia is mediated through a di-synaptic thalamic pathway which when severed is effective in alleviating dystonia. Our results provide a unifying hypothesis for the involvement of cerebellum and basal ganglia in generation of dystonia and suggest therapeutic strategies for the treatment of RDP. 2011-02-06 2011-03 /pmc/articles/PMC3430603/ /pubmed/21297628 http://dx.doi.org/10.1038/nn.2753 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Calderon, D. Paola
Fremont, Rachel
Kraenzlin, Franca
Khodakhah, Kamran
The neural substrates of Rapid-Onset Dystonia-Parkinsonism
title The neural substrates of Rapid-Onset Dystonia-Parkinsonism
title_full The neural substrates of Rapid-Onset Dystonia-Parkinsonism
title_fullStr The neural substrates of Rapid-Onset Dystonia-Parkinsonism
title_full_unstemmed The neural substrates of Rapid-Onset Dystonia-Parkinsonism
title_short The neural substrates of Rapid-Onset Dystonia-Parkinsonism
title_sort neural substrates of rapid-onset dystonia-parkinsonism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430603/
https://www.ncbi.nlm.nih.gov/pubmed/21297628
http://dx.doi.org/10.1038/nn.2753
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