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パーキンソン病および関連神経変性疾患のPET酸化ストレスイメージング

Publicly Offered Research

Project AreaBrain Environment
Project/Area Number 24111517
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionFukui Prefectural University (2013)
University of Fukui (2012)

Principal Investigator

米田 誠  福井県立大学, 看護福祉学部, 教授 (70270551)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywords酸化ストレス / PET / 脳機能イメージング / パーキンソン病 / ALS
Research Abstract

PET用核種標識化合物である62Cu-ATSMよって,ミトコンドリア呼吸鎖不全による過還元状態が惹起する活性酸素種の発生増加(酸化ストレス)を生体にて画像化することを可能にした.孤発性パーキンソン病(PD)患者において,62Cu-ATSM PETでの脳線条体での集積増加と,集積と臨床的重症度に正の相関関係を報告している.
平成25年度は,PD関連神経変性疾患と筋萎縮性側索硬化症(ALS)での酸化ストレスの関与を検討した.現在までに,①多系統萎縮症(MSA)患者9名と②ALS患者12名(年齢平均65.2歳,罹病平均期間25.8月,重症度スケールALSFRS-R平均30.9/48点),③Parkin遺伝子変異を有する家族性PD患者2名と家族性PD患者2名(順天堂大学脳神経内科との共同研究)を検討した.その結果,①MSA患者群では今のところ明らかな集積増加は認められず,PD患者との差は見出されなかった.②ALS患者群では,両側大脳皮質運動野に集積の有意な増加傾向が認められ(p<0.001),臨床重症度との相関(p<0.05),加齢との正の相関(p<0.05)が認められ,酸化ストレスの病態への関与が認められた.また,③Parkin遺伝子変異を有する家族性PD患者では,線条体への集積を認めた.
また,脳神経疾患における酸化ストレスの基礎研究として,ミトコンドリア病患者の血中の酸化ストレスの検討を行った.ミトコンドリア病の原因となるミトコンドリア遺伝子A3243G変異を有する患者14名と,健常者34名に対し採血を行い,d-ROMsによる酸化ストレスと,BAPによる抗酸化力の測定を行った.その結果,d-ROMsは,健常者群に比べて患者群で有意に増加していた(P<0.005).

Current Status of Research Progress
Reason

25年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

25年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (15 results)

All 2014 2013 2012

All Journal Article (8 results) (of which Peer Reviewed: 5 results) Presentation (7 results) (of which Invited: 3 results)

  • [Journal Article] Haploinsufficiency of CSF-1R and clinicopathological characterization in patients with HDLS.2014

    • Author(s)
      Konno T, Tada M, Tada M, Koyama A, Nozaki H, Harigaya Y, Nishimiya J, Matsunaga A, Yoshikura N, Ishihara K, Arakawa M, Isami A, Okazaki K, Yokoo H, Ihoh K, Yoneda M, Kawamura M, Inuzuka T, Takahashi H, Nishizawa M, Onodera O, Kakita A, Ikeuchi T
    • Journal Title

      Neurology

      Volume: 82 Issue: 2 Pages: 139-148

    • DOI

      10.1212/wnl.0000000000000046

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of preclinically latent hyperperfusion due to stroke-like episodes by arterial spin-labeling perfusion MRI in MELAS patients.2013

    • Author(s)
      Masamichi Ikawa, Makoto Yoneda, Tomoko Muramatsu, Akiko Matsunaga, Tetsuya Tsujikawa, Tatsuya Yamamoto, Nobuyuki Kosaka, Kazuyuki Kinoshita, Osamu Yamamura, Tadanori Hamano, Yasunari Nakamoto, Hirohiko Kimura
    • Journal Title

      Mitochondrion

      Volume: 13(6) Issue: 6 Pages: 676-680

    • DOI

      10.1016/j.mito.2013.09.007

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 62Cu-ATSM PET.神経内科検査のみかた―脳のイメージングを中心に2013

    • Author(s)
      井川正道,岡沢秀彦,米田誠
    • Journal Title

      Modern Physician

      Volume: 33 Pages: 577-579

    • Related Report
      2013 Annual Research Report
  • [Journal Article] ミトコンドリア心筋症2013

    • Author(s)
      井川正道,米田誠,田中雅嗣
    • Journal Title

      循環器内科

      Volume: 72 Pages: 592-598

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Evaluation of systemic redox states in patients carrying MELAS A3243G mutation in mitochondrial DNA.2012

    • Author(s)
      Masamichi Ikawa, Kenichiro Arakawa, Tadanori Hamano, Miwako Nagata, Yasunari Nakamoto, Masaru Kuriyama, Yasutoshi Koga, Makoto Yoneda.
    • Journal Title

      European Neurology

      Volume: 67(4) Issue: 4 Pages: 232-7

    • DOI

      10.1159/000336568

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crossed cerebellar hyperperfusion after MELAS attack followed up by whole brain continuous arterial spin labeling perfusion imaging2012

    • Author(s)
      Tsujikawa T, Yamamoto T, Ikawa M, Yoneda M, Kimura H
    • Journal Title

      Acta Radiol.

      Volume: 53 Issue: 2 Pages: 220-222

    • DOI

      10.1258/ar.2011.110274

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo functional brain imaging and a therapeutic trial of L-arginine in MELAS patients.2012

    • Author(s)
      Yoneda M, Ikawa M, Arakawa K, Kudo T, Kimura H, Fujibayashi Y, Okazawa H
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1820 Pages: 615-618

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ミトコンドリア心筋症.2012

    • Author(s)
      井川正道,米田誠,田中雅嗣
    • Journal Title

      循環器内科

      Volume: 72 Pages: 592-598

    • Related Report
      2012 Annual Research Report
  • [Presentation] Regional changes in cerebral oxidative stress of neurodegenerative disease evaluated by 62Cu-ATSM PET.2014

    • Author(s)
      Makoto Yoneda
    • Organizer
      International workshop on molecular functional imaging for brain and gynecologic oncology
    • Place of Presentation
      Fukui, Japan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Increased cerebral oxidative stress in amyotrophic lateral sclerosis: a 62Cu-ATSM PET study.2014

    • Author(s)
      Masamichi Ikawa, Hidehiko Okazawa, Tetsuya Tsujikawa, Tomoko Muramatsu, Toru Kishitani, Tomoko Kamisawa, Akiko Matsunaga, Osamu Yamamura, Tetsuya Mori, Tadanori Hamano, Yasushi Kiyono, Yasunari Nakamoto, Makoto Yoneda
    • Organizer
      The 66th Annual Meeting of AAN
    • Place of Presentation
      Philadelphia, PA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Pathophysiological decrease in the regional cerebral blood flow in pure autonomic failure with Lewy body.2014

    • Author(s)
      Tomoko Kamisawa, Masamichi Ikawa, Yuki Saito, Tomoko Muramatsu, Akiko Matsunaga, Osamu Yamamura, Tadanori Hamano, Yasunari Nakamoto, Shigeo Murayama, Hidehiko Okazawa, Makoto Yoneda
    • Organizer
      The 66th Annual Meeting of AAN
    • Place of Presentation
      Philadelphia, PA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] PET imaging of oxidative stress in neurodegenevative disorder.2013

    • Author(s)
      Makoto Yoneda
    • Organizer
      International Symposium on Mitochondria 2013
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] PET Imaging of oxidative stress in neurodegenerative diseases using 62Cu-ATSM.2012

    • Author(s)
      Makoto Yoneda
    • Organizer
      International Symposium of Asian Association of Aging Research2012
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2012-08-24
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] In vitro imaging of over-reduction state (oxidative stress) in cells with mitochondrial dysfunction using PET radiopharmaceutical Cu-ATSM.2012

    • Author(s)
      Masamichi Ikawa, Yukie Yoshii, Yasunari Nakamoto, Hidehiko Okazawa, Yasuhisa Fujibayashi, Makoto Yoneda
    • Organizer
      International Symposium of Asian Association of Aging Research, 2012
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2012-08-24
    • Related Report
      2012 Annual Research Report
  • [Presentation] PET Imaging of Striatal Oxidative Stress in Patients with Parkinson's Disease using 62Cu-ATSM.2012

    • Author(s)
      Masamichi Ikawa, Hidehiko Okazawa, Takashi Kudo, Yasunari Nakamoto, Yasuhisa Fujibayashi, Makoto Yoneda
    • Organizer
      The 64th Annual Meeting of AAN
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2012-04-21
    • Related Report
      2012 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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