ArticleNeurobiology of disease2015
Aberrant Purkinje cell activity is the cause of dystonia in a shRNA-based mouse model of Rapid Onset Dystonia-Parkinsonism.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
- Metabolic and Volumetric Alterations in the Basal Ganglia and the Cerebellum in Dopa-Responsive Dystonia in Symptomatic and Asymptomatic GCH1 Mutation Carriers.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Cerebellar motor and non-motor contributions to dystonia pathophysiology and treatment.Dystonia (Lausanne, Switzerland) · 2026Article
- Cerebellar and extra-cerebellar symptoms in movement disorders.Arquivos de neuro-psiquiatria · 2025Review
- Cerebellar contributions to dystonia: unraveling the role of Purkinje cells and cerebellar nuclei.Dystonia (Lausanne, Switzerland) · 2025Article
- eIF2α phosphorylation evokes dystonia-like movements with D2-receptor and cholinergic origin and abnormal neuronal connectivity.bioRxiv : the preprint server for biology · 2024Article
- Physiological Recordings of the Cerebellum in Movement Disorders.Cerebellum (London, England) · 2023Review
- Cerebellar Dysfunction as a Source of Dystonic Phenotypes in Mice.Cerebellum (London, England) · 2023Article
- T-type calcium channels as therapeutic targets in essential tremor and Parkinson's disease.Annals of clinical and translational neurology · 2023Review
- Cerebellar dysfunction in rodent models with dystonia, tremor, and ataxia.Dystonia (Lausanne, Switzerland) · 2023Article
- DYT-Frontiers in neuroscience · 2023Review
- Synaptic Dysfunction in Dystonia: Update From Experimental Models.Current neuropharmacology · 2023Review
- Potential interactions between cerebellar dysfunction and sleep disturbances in dystonia.Dystonia (Lausanne, Switzerland) · 2022Article
- Cerebellar neuronal dysfunction accompanies early motor symptoms in spinocerebellar ataxia type 3.Disease models & mechanisms · 2022Article
- Cerebellar stimulation prevents Levodopa-induced dyskinesia in mice and normalizes activity in a motor network.Nature communications · 2022Article
- Comparative description of the mRNA expression profile of NaThe Journal of comparative neurology · 2022Article
- Cerebellum Involvement in Dystonia During Associative Motor Learning: Insights From a Data-Driven Spiking Network Model.Frontiers in systems neuroscience · 2022Article
- Quantification of Behavioral Deficits in Developing Mice With Dystonic Behaviors.Dystonia (Lausanne, Switzerland) · 2022Article
- Dystonia and Cerebellum: From Bench to Bedside.Life (Basel, Switzerland) · 2021Review
- Contemporary functional neuroanatomy and pathophysiology of dystonia.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- Abnormal cerebellar function and tremor in a mouse model for non-manifesting partially penetrant dystonia type 6.The Journal of physiology · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Loss-of-function mutations in the α3 isoform of the sodium pump are responsible for Rapid Onset Dystonia-Parkinsonism (RDP). A pharmacologic model of RDP replicates the most salient features of RDP, and implicates both the cerebellum and basal ganglia in the disorder; dystonia is associated with aberrant cerebellar output, and the parkinsonism-like features are attributable to the basal ganglia. The pharmacologic agent used to generate the model, ouabain, is selective for sodium pumps. However, close to the infusion sites in vivo it likely affects all sodium pump isoforms. Therefore, it remains to be established whether selective loss of α3-containing sodium pumps replicates the pharmacologic model. Moreover, while the pharmacologic model suggested that aberrant firing of Purkinje cells was the main cause of abnormal cerebellar output, it did not allow the scrutiny of this hypothesis. To address these questions RNA interference using small hairpin RNAs (shRNAs) delivered via adeno-associated viruses (AAV) was used to specifically knockdown α3-containing sodium pumps in different regions of the adult mouse brain. Knockdown of the α3-containing sodium pumps mimicked both the behavioral and electrophysiological changes seen in the pharmacologic model of RDP, recapitulating key aspects of the human disorder. Further, we found that knockdown of the α3 isoform altered the intrinsic pacemaking of Purkinje cells, but not the neurons of the deep cerebellar nuclei. Therefore, acute knockdown of proteins associated with inherited dystonias may be a good strategy for developing phenotypic genetic mouse models where traditional transgenic models have failed to produce symptomatic mice.
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