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Development of new surgical therapies for l-dopa induced dyskinesia targeting striatal striosome comparment

Research Project

Project/Area Number 17K10899
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionThe University of Tokushima

Principal Investigator

MORIGAKI Ryoma  徳島大学, 病院, 助教 (70710565)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords不随意運動 / ジスキネジア / 動物モデル / 線条体 / ジストニア / パーキンソン病 / ハンチントン舞踏病 / げっ歯類 / 治療法 / ストリオソーム / 線条体ストリオソーム分画 / 脳内ネットワーク / 脳深部刺激療法 / 脳神経疾患
Outline of Final Research Achievements

After establishing l-dopa induced dyskinesia Parkinson's disease rat model, I tried to modulate the function of the striosome compartment in the striatum by destroying the infralimbic cortex. But it had no therapeutic effects on dyskinesia. Then, I underwent tracing studies using AAV-DJ virus in order to find the cortex area which innervates striosome compartment in the dorsolateral striatum. I am also checking if there is an abnormality in the striosome compartment of other movement disorder mice models, i.e. q175 mice model of Huntington's disease and dystonia model mice generated by ouabain in the cerebellum. These studies are still on-going.

Academic Significance and Societal Importance of the Research Achievements

L-ドーパ誘発性ジスキネジアモデルラットに関しては本プロトコールでは3週間でモデルが確立することが明らかになり、今後の研究に生かされる可能性があった。Infralimbic cortex破壊によるジスキネジア抑制実験はうまくいかなかったが、その検討から線条体ストリオソームに投射する新たな領域を見つけつつある。また、q175ハンチントン舞踏病マウスモデルにおいてストリオソーム分画に異常が起こっていることを発見し、不随意運動症に関して線条体ストリオソーム分画の異常が関与していることを示唆した。今後の研究、治療に役立つ可能性を提示できた。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] Massachusetts Institute of Technology(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Massachussetts Institute of Technology(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] West Visayas State University(フィリピン)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Massachusetts Institute of Technology(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Regional difference in energy metabolism in murine hippocampus2019

    • Author(s)
      Tokumaru O, Goto M, Abe S, Tandai-Hiruma M, Maruyama S, Kemuriyama T, Ogata K, Eshima N, Kitano T, Setou M, Nishida Y
    • Journal Title

      Journal of Cerebral Blood Flow & Metabolism

      Volume: 39 Issue: 1_suppl Pages: 204-205

    • DOI

      10.1177/0271678x19851020

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Turning on the Left Side Electrode Changed Depressive State to Manic State in a Parkinson's Disease Patient Who Received Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Case Report2018

    • Author(s)
      Kinoshita Makoto、Nakataki Masahito、Morigaki Ryoma、Sumitani Satsuki、Goto Satoshi、Kaji Ryuji、Ohmori Tetsuro
    • Journal Title

      Clinical Psychopharmacology and Neuroscience

      Volume: 16 Issue: 4 Pages: 494-496

    • DOI

      10.9758/cpn.2018.16.4.494

    • NAID

      120006808638

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phenotype variability and allelic heterogeneity in KMT2B-Associated disease.2018

    • Author(s)
      Kawarai T, Miyamoto R, Nakagawa E, Koichihara R, Sakamoto T, Mure H, Morigaki R, Koizumi H, Oki R, Montecchiani C, Caltagirone C, Orlacchio A, Hattori A, Mashimo H, Izumi Y, Mezaki T, Kumada S, Taniguchi M, Yokochi F, Saitoh S, Goto S, Kaji R
    • Journal Title

      Parkinsonism Relat Disord.

      Volume: 18 Pages: 30137-30138

    • DOI

      10.1016/j.parkreldis.2018.03.022

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Striatal vulnerability in Huntington's disease neuroprotection versus neurotoxicity2017

    • Author(s)
      Ryoma Morigaki, Satoshi Goto
    • Journal Title

      Brain Sciences

      Volume: 7 Issue: 6 Pages: 1-25

    • DOI

      10.3390/brainsci7060063

    • NAID

      120006808636

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicopathological phenotype and genetics of X-linked dystonia-parkinsonism (XDP; DYT3; Lubag)2017

    • Author(s)
      Toshitaka Kawarai, Ryoma Morigaki, Ryuji Kaji, Satoshi Goto
    • Journal Title

      Brain Sciences

      Volume: 7 Issue: 7 Pages: 1-13

    • DOI

      10.3390/brainsci7070072

    • NAID

      120006808637

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] GPi-DBSを施行したDYT-GNAL(DYT25)の一例2020

    • Author(s)
      森垣 龍馬, 牟礼 英生, 松田 拓, 宮本 亮介, 山本 陽子, 豊田 直人, 髙木 康志, 後藤 惠
    • Organizer
      第59回日本定位・機能神経外科学会(浜松)
    • Related Report
      2019 Annual Research Report
  • [Presentation] FDG PETを用いたジストニア患者の脳代謝ネットワークパターンの描出2020

    • Author(s)
      牟礼 英生, 藤田 浩司, 森垣 龍馬, 宮本 亮介, 松田 拓, 後藤 惠, 髙木 康志
    • Organizer
      第59回日本定位・機能神経外科学会(浜松)
    • Related Report
      2019 Annual Research Report
  • [Presentation] ジストニアと強迫性障害の関係についての検討2020

    • Author(s)
      松田 拓, 森垣 龍馬, 牟礼 英生, 中瀧 理仁, 山本 陽子, 豊田 直人, 後藤 惠, 髙木 康志
    • Organizer
      第59回日本定位・機能神経外科学会(浜松)
    • Related Report
      2019 Annual Research Report
  • [Presentation] ロボットスーツHALを用いた脳卒中急性期リハビリテーションの当院での取り組み2020

    • Author(s)
      松田 拓, 鹿草 宏, 梅村 公子, 佐藤 紀, 森垣 龍馬, 牟礼 英生, 兼松 康久, 松元 友暉, 原田 雅史, 加藤 真介, 髙木 康志
    • Organizer
      第8回日本脳神経HAL研究会(福岡)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Mu opioid receptors are strongly upregulated in the q175 mouse model of huntingtons disease2019

    • Author(s)
      Ryoma Morigaki, Lee H Janifer, Yoshida Tomoko, Wuthrich Christian and Graybiel M Ann
    • Organizer
      Neuroscience 2019 (Chicago)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Olfactory type G-protein alfa subunit related changes in the striatum underlie the genesis of L-dopa-induced dyskinesia2019

    • Author(s)
      Ryoma Morigaki, Shinya Ohkita, Hideo Mure, Yasushi Takagi and Satoshi Goto
    • Organizer
      Brain and Brain PET 2019 (Tokyo)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 機能性ジストニアは器質性ジストニアスペクトラム障害か?2019

    • Author(s)
      森垣 龍馬, 牟礼 英生, 宮本 亮介, 松田 拓, 山本 陽子, 髙木 康志, 後藤 惠
    • Organizer
      日本脳神経外科学会第78回学術集会(大阪)
    • Related Report
      2019 Annual Research Report
  • [Presentation] FDG PETを用いたジストニア患者の脳代謝ネットワークパターンの描出2019

    • Author(s)
      牟礼 英生, 藤田 浩司, 森垣 龍馬, 宮本 亮介, 後藤 惠, 髙木 康志
    • Organizer
      日本脳神経外科学会第78回学術集会(大阪)
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2022-02-21  

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