• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Long-term oral administration of the NMDA receptor antagonist memantine extends life span in spinocerebellar ataxia type 1 knock-in mice.

Research Project

Project/Area Number 25830046
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurochemistry/Neuropharmacology
Research InstitutionGunma University

Principal Investigator

IIZUKA Akira  群馬大学, 医学(系)研究科(研究院), 研究員 (10466683)

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)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
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)
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
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.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (4 results)

All 2015 2013 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) Remarks (1 results)

  • [Journal Article] Long-term oral administration of the NMDA receptor antagonist memantine extends life span in spinocerebellar ataxia type 1 knock-in mice.2015

    • Author(s)
      Akira Iizuka, Kazuhiro Nakamura, Hirokazu Hirai
    • Journal Title

      Neuroscience letters

      Volume: 592 Pages: 37-41

    • DOI

      10.1016/j.neulet.2015.02.055

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mesenchymal Stem Cells Ameliorate Cerebellar Pathology in a Mouse Model of Spinocerebellar Ataxia Type 1.2013

    • Author(s)
      Matsuura S, Shuvaev AN, Iizuka A, Nakamura K, Hirai H.
    • Journal Title

      Cerebellum

      Volume: epub Issue: 3 Pages: 323-330

    • DOI

      10.1007/s12311-013-0536-1

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] NMDA受容体拮抗薬メマンチンの長期経口投与によるSCA1モデルマウス病態の改善2015

    • Author(s)
      Akira Iizuka, Kazuhiro Nakamura, Hirokazu Hirai
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸国際展示場
    • Year and Date
      2015-07-28 – 2015-07-31
    • Related Report
      2014 Annual Research Report
  • [Remarks] Publications

    • URL

      http://synapse.dept.med.gunma-u.ac.jp/?post_type=publications-type

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi