2013 Fiscal Year Final Research Report
Analysis of synapse pathology underlying the spinocerebellar ataxia
| Project/Area Number |
24800008
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | Gunma University |
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Principal Investigator |
SHUVAEV Anton 群馬大学, 医学(系)研究科(研究院), 研究員 (30633771)
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| Project Period (FY) |
2012-08-31 – 2014-03-31
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| Keywords | spinocerebellar ataxia / cerebellum / Purkinje cell / glutamate receptor / patch clamp |
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| Research Abstract |
Staggerer mutant mice, which show severe cerebellar ataxia, are caused by functional loss of a nuclear transcription factor, retinoid-related orphan receptor alpha (RORalpha) and exhibit complete loss of metabotropic glutamate receptor subtype 1 (mGluR1)-mediated signaling in Purkinje cells. It has been shown that model mice of spinocerebellar ataxia type 1 (SCA1 mice) express significantly lower levels of RORalpha in Purkinje cells and therefore, we hypothesized that mGluR signaling was impaired also in SCA1 mice. Our electrophysiology experiments revealed significant defects of mGluR signaling in SCA1 mice. Moreover, a pharmacological treatment that enhanced mGluR signaling improved cerebellar motor learning in SCA1 mice. These results suggest the potential therapeutic intervention for SCA1 patients through mGluR1.
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[Journal Article] Mutant Ataxin-3 with an Abnormally Expanded Polyglutamine Chain Disrupts Dendritic Development and Metabotropic Glutamate Receptor Signaling in Mouse Cerebellar Purkinje Cells2014
Author(s)
Konno A, Shuvaev AN, Miyake N, Miyake K, Iizuka A, Matsuura S, Huda F, Nakamura K, Yanagi S, Shimada T, and Hirai H
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Journal Title
Cerebellum
Volume: 13(1)
Pages: 29-41
Peer Reviewed
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