ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Spinocerebellar ataxia type 6 protein aggregates cause deficits in motor learning and cerebellar plasticity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 69 citations in OpenAlex.
- Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias.Cell death & disease · 2025Review
- A novel early onset spinocerebellar ataxia 13 BAC mouse model with cerebellar atrophy, tremor, and ataxic gait.Experimental animals · 2025Article
- Ablation of TrkB from Enkephalinergic Precursor-Derived Cerebellar Granule Cells Generates Ataxia.Biology · 2024Article
- A combination of chlorzoxazone and folic acid improves recognition memory, anxiety and depression in SCA3-84Q mice.Human molecular genetics · 2024Article
- Phenotypic analysis of ataxia in spinocerebellar ataxia type 6 mice using DeepLabCut.Scientific reports · 2024Article
- Mild Deficits in Fear Learning: Evidence from Humans and Mice with Cerebellar Cortical Degeneration.eNeuro · 2024Article
- Mitochondrial damage and impaired mitophagy contribute to disease progression in SCA6.Acta neuropathologica · 2024Article
- Article
- Development and validation of an ultrahigh-performance liquid chromatography-tandem mass spectrometry method to investigate the plasma pharmacokinetics of a KRapid communications in mass spectrometry : RCM · 2023Article
- Loss-of-function KAmerican journal of physiology. Cell physiology · 2023Article
- Cerebellar contribution to threat probability in a SCA6 mouse model.Human molecular genetics · 2022Article
- Electrophysiological Studies Support Utility of Positive Modulators of SK Channels for the Treatment of Spinocerebellar Ataxia Type 2.Cerebellum (London, England) · 2022Review
- Article
- Deletion of the P/Q-Type Calcium Channel from Serotonergic Neurons Drives Male Aggression in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications.Cerebellum (London, England) · 2022Article
- Controlling absence seizures from the cerebellar nuclei via activation of the GCellular and molecular life sciences : CMLS · 2022Article
- The Clinical Concept of LTDpathy: Is Dysregulated LTD Responsible for Prodromal Cerebellar Symptoms?Brain sciences · 2022Article
- What is the Pathogenic CAG Expansion Length in Huntington's Disease?Journal of Huntington's disease · 2021Review
- In vivo analysis of the spontaneous firing of cerebellar Purkinje cells in awake transgenic mice that model spinocerebellar ataxia type 2.Cell calcium · 2021Article
- The Optogenetic Revolution in Cerebellar Investigations.International journal of molecular sciences · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinocerebellar ataxia type 6 (SCA6) is linked to poly-glutamine (polyQ) within the C terminus (CT) of the pore-forming subunits of P/Q-type Ca(2+) channels (Cav2.1) and is characterized by CT protein aggregates found in cerebellar Purkinje cells (PCs). One hypothesis regarding SCA6 disease is that a CT fragment of the Cav2.1 channel, which is detected specifically in cytosolic and nuclear fractions in SCA6 patients, is associated with the SCA6 pathogenesis. To test this hypothesis, we expressed P/Q-type channel protein fragments from two different human CT splice variants, as predicted from SCA6 patients, in PCs of mice using viral and transgenic approaches. These splice variants represent a short (CT-short without polyQs) and a long (CT-long with 27 polyQs) CT fragment. Our results show that the different splice variants of the CTs differentially distribute within PCs, i.e., the short CTs reveal predominantly nuclear inclusions, whereas the long CTs prominently reveal both nuclear and cytoplasmic aggregates. Postnatal expression of CTs in PCs in mice reveals that only CT-long causes SCA6-like symptoms, i.e., deficits in eyeblink conditioning (EBC), ataxia, and PC degeneration. The physiological phenotypes associated specifically with the long CT fragment can be explained by an impairment of LTD and LTP at the parallel fiber-to-PC synapse and alteration in spontaneous PC activity. Thus, our results suggest that the polyQ carrying the CT fragment of the P/Q-type channel is sufficient to cause SCA6 pathogenesis in mice and identifies EBC as a new diagnostic strategy to evaluate Ca(2+) channel-mediated human diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.