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Mechanism of activity-dependent motor improvement in SCA

Research Project

Project/Area Number 17K07103
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionGunma University

Principal Investigator

Hosoi Nobutake  群馬大学, 大学院医学系研究科, 准教授 (90543570)

Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords小脳 / baclofen / GABAb受容体 / 活動依存的 / 脊髄小脳失調症 / プルキンエ細胞 / GABAb受容体 / リハビリ
Outline of Final Research Achievements

In this study, I focused on congenital spinocerebellar ataxia (SCA) which is characterized by cerebellar dysfunction, and the purpose of the study was examining the mechanism by which oral administration of low-dose baclofen may improve motor performance of SCA model mice in an activity-dependent manner. To this end, I tried to develop a technique for activity-dependent labeling of cerebellar neurons, but it turned out to be difficult because of the unstableness and the low efficiency of activity-dependent labeling in the cerebellum. The effect of low-dose baclofen on cerebellar function was examined, and the results suggest that baclofen might act on the brain regions other than the cerebellum to improve motor performance of SCA3 model mice.

Academic Significance and Societal Importance of the Research Achievements

脊髄小脳失調症(SCA)は、治療法として対症療法しかない難病指定の希少疾患であるため、SCAの治療法に関する研究は大きな社会的意義がある。小脳神経細胞を活動依存的にラベリングする新しい手法の適用はうまくいかなかったものの、SCA3モデルマウスでは、低濃度バクロフェンの作用が小脳以外のところで作用して運動機能の改善に関与する可能性を得られたことは、学術的にも意義があると思われる。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2022 2021 2020 2019 2018 2017 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Remarks (2 results)

  • [Journal Article] Electrophysiological and Imaging Analysis of GFP-Tagged Protein Kinase C γ Translocation in Cerebellar Purkinje Cells2022

    • Author(s)
      Hirai H, Fukai Y, Konno A, Hosoi N.
    • Journal Title

      Cerebellum

      Volume: - Issue: 5 Pages: 776-783

    • DOI

      10.1007/s12311-022-01384-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protein kinase Cγ in cerebellar Purkinje cells regulates Ca 2+-activated large-conductance K + channels and motor coordination2022

    • Author(s)
      Watanave M, Takahashi N, Hosoi N, Konno A, Yamamoto H, Yasui H, Kawachi M, Horii T, Matsuzaki Y, Hatada I, Hirai H.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 119(7) Issue: 7

    • DOI

      10.1073/pnas.2113336119

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The neurotoxic effect of lactational PFOS exposure on cerebellar functional development in male mice2022

    • Author(s)
      Ninomiya A, Mshaty A, Haijima A, Yajima H, Kokubo M, Khairinisa MA, Ariyani W, Fujiwara Y, Ishii S, Hosoi N, Hirai H, Amano I, Koibuchi N.
    • Journal Title

      Food Chem Toxicol

      Volume: 159:112751 Pages: 112751-112751

    • DOI

      10.1016/j.fct.2021.112751

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GABAergic neuron-specific whole-brain transduction by AAV-PHP.B incorporated with a new GAD65 promoter2021

    • Author(s)
      Hoshino Chiaki、Konno Ayumu、Hosoi Nobutake、Kaneko Ryosuke、Mukai Ryo、Nakai Junichi、Hirai Hirokazu
    • Journal Title

      Molecular Brain

      Volume: 14 Issue: 1 Pages: 1-18

    • DOI

      10.1186/s13041-021-00746-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deletion of Class II ADP-Ribosylation Factors in Mice Causes Tremor by the Nav1.6 Loss in Cerebellar Purkinje Cell Axon Initial Segments.2019

    • Author(s)
      Hosoi N, Shibasaki K, Hosono M, Konno A, Shinoda Y, Kiyonari H, Inoue K, Muramatsu SI, Ishizaki Y, Hirai H, Furuichi T, Sadakata T
    • Journal Title

      J Neurosci

      Volume: 39(32) Issue: 32 Pages: 6339-6353

    • DOI

      10.1523/jneurosci.2002-18.2019

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 甲状腺ホルモンシグナルによる小脳シナプス可塑性の調節メカニズム2021

    • Author(s)
      細井延武、二ノ宮彩音、小久保倫史、天野出月、平井宏和、鯉淵典之
    • Organizer
      第99回日本生理学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Deletion of class II ARFs causes tremor by disruption of Nav1.6 localization to the axon initial segment of cerebellar Purkinje cells in mice2020

    • Author(s)
      Nobutake Hosoi, Koji Shibasaki, Teiichi Furuichi, Hirokazu Hirai, Tetsushi Sadakata
    • Organizer
      FENS 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Insufficiency of class II ARFs causes tremor by impairment of Nav1.6 localization to the axon initial segment of cerebellar Purkinje cells in mice2020

    • Author(s)
      細井延武、柴崎貢志、古市貞一、平井宏和、定方哲史
    • Organizer
      生理研研究会 2020 シナプス研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] クラスIIARFはNav1.6を小脳プルキンエ細胞の軸索初節部に局在させる新規な役割を持つ2020

    • Author(s)
      細井延武、柴崎貢志、古市貞一、平井宏和、定方哲史
    • Organizer
      第98回日本生理学会大会 Web開催
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] クラスII ARFタンパク質の欠失はNav1.6の輸送不全により振戦を発症させる2019

    • Author(s)
      定方 哲史、細井 延武、柴崎 貢志、今野 歩、平井 宏和、石崎 泰樹、古市 貞一
    • Organizer
      第42回 日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Presentation] クラスIIARF不全で動作時振戦を示すマウスの小脳プルキンエ細胞における活動電位発火とNa電流:クラスIIARFがNav1.6を軸索起始部へ局在させる役割を持つ可能性2019

    • Author(s)
      細井 延武、柴崎 貢志、古市 貞)、平井 宏和、定方 哲史
    • Organizer
      第97回 日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 甲状腺ホルモン受容体による小脳プルキンエ細胞におけるシナプス可塑性の調節機構2019

    • Author(s)
      二ノ宮 彩音、細井 延武、小久保 倫文、天野 出月、蓜島 旭、宮崎 航、 平井 宏和、鯉淵 典之
    • Organizer
      第97回 日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] The effect of orally-administered baclofen on spinocerebellar ataxia type 3 (SCA3) model mice2018

    • Author(s)
      Nobutake Hosoi and Hirokazu Hirai
    • Organizer
      FAOPS 2019 (第96回日本生理学会大会・第9回アジア・オセアニア生理学会連合大会 合同大会)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 低濃度GABAb受容体アゴニスト投与による遺伝性脊髄小脳変性症1型(SCA1)モデルマウスの運動機能の改善2017

    • Author(s)
      細井 延武、 アントン シュワエフ、 平井 宏和
    • Organizer
      第40回 日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Pros and cons of an AAV double infection method combined with Tet system: an experimental study2017

    • Author(s)
      Nobutake Hosoi, Masayuki Shichida, Ayumu Konno and Hirokazu Hirai
    • Organizer
      Neuroscienc 2017 SfN annual meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 遺伝性脊髄小脳変性症に対するGPCRクロストークを利用した治療戦略2017

    • Author(s)
      細井 延武
    • Organizer
      第9回 光操作研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] GPCR(Gタンパク共役型受容体)クロストークを利用した脊髄小脳失調症(SCA1)に対する治療可能性2017

    • Author(s)
      細井 延武、 アントン シュワエフ、 平井 宏和
    • Organizer
      第95回 日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Remarks] 【医学系研究科】体が震える原因を解明 (群馬大学 webページ 新着情報)

    • URL

      https://www.gunma-u.ac.jp/information/54661

    • Related Report
      2019 Research-status Report
  • [Remarks] 体が震える原因を解明 (群馬大学大学院医学系研究科 webページ ニュースリリース )

    • URL

      https://www.med.gunma-u.ac.jp/newsrelease/6209.html

    • Related Report
      2019 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2023-01-30  

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