ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Prolonged Type 1 Metabotropic Glutamate Receptor Dependent Synaptic Signaling Contributes to Spino-Cerebellar Ataxia Type 1.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
- Enhanced mGluR1 function causes motor deficits and region-specific Purkinje cell dysfunction.Brain : a journal of neurology · 2026Article
- Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias.Cell death & disease · 2025Review
- Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1.Neuron · 2024Article
- Review
- Pathophysiology of Cerebellar Degeneration in Mitochondrial Disorders: Insights from theInternational journal of molecular sciences · 2023Article
- Therapeutic Strategies for Spinocerebellar Ataxia Type 1.Biomolecules · 2023Review
- Optogenetic activation of mGluR1 signaling in the cerebellum induces synaptic plasticity.iScience · 2023Article
- Viewpoint: spinocerebellar ataxias as diseases of Purkinje cell dysfunction rather than Purkinje cell loss.Frontiers in molecular neuroscience · 2023Review
- Article
- Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology.Brain sciences · 2022Review
- The Clinical Concept of LTDpathy: Is Dysregulated LTD Responsible for Prodromal Cerebellar Symptoms?Brain sciences · 2022Article
- Nitric Oxide Critically Regulates Purkinje Neuron Dendritic Development Through a Metabotropic Glutamate Receptor Type 1-Mediated Mechanism.Cerebellum (London, England) · 2020Article
- Aberrant Cerebellar Circuitry in the Spinocerebellar Ataxias.Frontiers in neuroscience · 2020Review
- Modulation of Increased mGluR1 Signaling by RGS8 Protects Purkinje Cells From Dendritic Reduction and Could Be a Common Mechanism in Diverse Forms of Spinocerebellar Ataxia.Frontiers in cell and developmental biology · 2020Article
- Emerging connections between cerebellar development, behaviour and complex brain disorders.Nature reviews. Neuroscience · 2019Review
- Spinocerebellar ataxias: prospects and challenges for therapy development.Nature reviews. Neurology · 2018Review
- Altered synaptic and firing properties of cerebellar Purkinje cells in a mouse model of ARSACS.The Journal of physiology · 2018Article
- Loss of cerebellar glutamate transporters EAAT4 and GLAST differentially affects the spontaneous firing pattern and survival of Purkinje cells.Human molecular genetics · 2018Article
- Protein kinase C activity is a protective modifier of Purkinje neuron degeneration in cerebellar ataxia.Human molecular genetics · 2018Article
- Targeting potassium channels to treat cerebellar ataxia.Annals of clinical and translational neurology · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledType 1 metabotropic glutamate receptor (mGluR1)-dependent signaling at parallel fiber to Purkinje neuron synapses is critical for cerebellar function. In a mouse model of human spino-cerebellar ataxia type 1 (early SCA1, 12 weeks) we find prolonged parallel fiber mGluR1-dependent synaptic currents and calcium signaling. Acute treatment with a low dose of the potent and specific activity-dependent mGluR1-negative allosteric modulator JNJ16259685 shortened the prolonged mGluR1 currents and rescued the moderate ataxia. Our results provide exciting new momentum for developing mGluR1-based pharmacology to treat ataxia. SIGNIFICANCE STATEMENT: Ataxia is a progressive and devastating degenerative movement disorder commonly associated with loss of cerebellar function and with no known cure. In the early stages of a mouse model of human spinocerebellar ataxia type 1, SCA1, where mice exhibit only moderate motor impairment, we detect excess "gain of function" of metabotropic glutamate receptor signaling at an important cerebellar synapse. Because careful control of this type of signaling is critical for cerebellar function in mice and humans, we sought to remove the excess signaling with a powerful, readily available pharmacological modulator. Remarkably, this pharmacological treatment acutely restored normal motor function in the ataxic mice. Our results pave the way for exploring a new avenue for early treatment of human ataxias.
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