Long-term oral administration of the NMDA receptor antagonist memantine extends life span in spinocerebellar ataxia type 1 knock-in mice.
| Project/Area Number |
25830046
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Gunma University |
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Principal Investigator |
IIZUKA Akira 群馬大学, 医学(系)研究科(研究院), 研究員 (10466683)
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| Co-Investigator(Renkei-kenkyūsha) |
HIRAI Hirokazu 群馬大学, 大学院医学系研究科, 教授 (70291086)
NAKAMURA Kazuhiro 群馬大学, 大学院医学系研究科, 准教授 (10327835)
KONNO Ayumu 群馬大学, 大学院医学系研究科, 助教 (40509048)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 脊髄小脳変性症1型 / メマンチン / NMDA受容体 / 小脳 / プルキンエ細胞 / 神経変性疾患 / 脊髄小脳変性症 / 神経変性症 |
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| Outline of Final Research Achievements |
Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by abnormal Sca1 gene. Although the mechanisms underlying the symptoms of SCA1 have not been determined, aberrant neuronal activation contributes to the neurodegenerative disorder. Here we examined the potential involvement of extrasynaptic N-methyl-d-aspartate receptor (NMDAR) activation in the pathogenesis of SCA1 by administering memantine, NMDAR antagonist, in SCA1 knock-in (KI) mice. Memantine was administered orally to the SCA1 KI mice from 4 weeks of age until death. The treatment significantly prolonged the life span of SCA1 KI mice. Furthermore, memantine significantly suppressed the loss of Purkinje cells in the cerebellum and motor neurons in the dorsal motor nucleus of the vagus. These findings support the contribution of aberrant activation of extrasynaptic NMDARs to neuronal cell death in SCA1 KI mice and suggest that memantine may also have therapeutic benefits in human SCA1 patients.
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Report
(3 results)
Research Products
(4 results)
