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New therapeutic strategy for refractory depression: analysis of neuron remodeling using stem cell treatment

Research Project

Project/Area Number 18K07569
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionSapporo Medical University

Principal Investigator

Kigawa Yoshiyasu  札幌医科大学, 医学部, 助教 (50581146)

Co-Investigator(Kenkyū-buntansha) 佐々木 祐典  札幌医科大学, 医学部, 准教授 (20538136)
橋本 恵理  札幌医科大学, 医学部, 准教授 (30301401)
鵜飼 渉  札幌医科大学, 医療人育成センター, 准教授 (40381256)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords難治性うつ病 / 骨髄間葉系幹細胞 / 神経回路リモデリング / FASD / 血中exosome / brain-derived exosome / miRNA / 幹細胞移植 / brain derived exosome / 難治性うつ病,
Outline of Final Research Achievements

For the purpose of establishing a new treatment method for refractory depression, we produced a refractory depression model rat via double stress exposure in which alcohol exposure is given during embryonic period and corticosterone is administered during adolescence. Using this model, we have conducted analysis of efficacies of psychiatric drug and BM-MSC administration for behaviors of social function (social interaction behavior) and sympathetic function (rescue behavior of others). The result demonstrated that the administration of MSCs specifically improved the social dysfunction of the refractory depression model, while the administration of the Chinese herbal medicine Kamikihito specifically improved and enhanced the empathic function of this model. Currently, we are proceeding the integrative analysis for their related brain function changes.

Academic Significance and Societal Importance of the Research Achievements

本研究の分担研究者は,本学医学部神経再生医療学部部門において,脊髄損傷後の麻痺症状に対する骨髄間葉系幹細胞による治療法についての研究を進めてきたが,既にその効果は臨床試験で確認され,実臨床への応用が始まった段階となっている。加えて,脳梗塞後の麻痺症状に対しての臨床試験が進行中であり,認知症に対しても同細胞を用いた臨床試験が予定されている状況にある。このような状況を踏まえると,投与する細胞の由来を骨髄間葉系幹細胞とした本研究の遂行は,その臨床応用の実現を格段に近づけるものであり,現在有効な治療法に乏しい難治性うつ病の患者への朗報となるとともに,社会的にも大きな貢献が期待できるものと確信している。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (20 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (7 results) (of which Int'l Joint Research: 1 results) Book (2 results)

  • [Int'l Joint Research] Department of Pharmacological/&Biomolecular Sciennce,/University of Milan(イタリア)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Diseases as the Target of Cellular Therapy with Mesenchymal Stem Cells.2020

    • Author(s)
      1)Sasaki M, Oka S, Kataoka-Sasaki Y, Kocsis JD, Honmou O.
    • Journal Title

      World Neurosurg.

      Volume: 135 Pages: 375-376

    • DOI

      10.1016/j.wneu.2019.12.137

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prolonged lifespan in a spontaneously hypertensive rat (stroke prone) model following intravenous infusion of mesenchymal stem cells2020

    • Author(s)
      Nakazaki Masahito、Oka Shinichi、Sasaki Masanori、Kataoka-Sasaki Yuko、Nagahama Hiroshi、Hashi Kazuo、Kocsis Jeffery D.、Honmou Osamu
    • Journal Title

      Heliyon

      Volume: 6 Issue: 12 Pages: e05833-e05833

    • DOI

      10.1016/j.heliyon.2020.e05833

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 高齢者脊椎疾患リハビリテーションアプローチ:高齢脊髄損傷患者のリハビリテーション医療-骨髄間葉系幹細胞移植治療との関連.2020

    • Author(s)
      廣田 亮介,佐々木 祐典,押切 勉,栗原 康太,本望 修,山下 敏彦.
    • Journal Title

      Medical Rehabilitation

      Volume: 249 Pages: 49-53

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Prevention of neointimal hyperplasia induced by an endovascular stent via intravenous infusion of mesenchymal stem cells.2019

    • Author(s)
      2)Nakazaki M, Oka S, Sasaki M, Kataoka-Sasaki Y, Onodera R, Komatsu K, Iihoshi S, Hiroura M, Kawaguchi A, Kocsis JD, Honmou O.
    • Journal Title

      J Neurosurg.

      Volume: 4 Issue: 6 Pages: 1-13

    • DOI

      10.3171/2019.7.jns19575

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intravenous infusion of mesenchymal stem cells improves impaired cognitive function in a cerebral small vessel disease model. Neuroscience.2019

    • Author(s)
      3)Nakazaki M, Sasaki M, Kataoka-Sasaki Y, Oka S, Suzuki J, Sasaki Y, Nagahama H, Hashi K, Kocsis JD, Honmou O.
    • Journal Title

      J Neuroscience.

      Volume: 408 Pages: 361-377

    • DOI

      10.1016/j.neuroscience.2019.04.018

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 運動器診療におけるプレシジョンメディシン:脊髄損傷への自己骨髄間葉系幹細胞を用いた再生医療.2019

    • Author(s)
      4)廣田 亮介,佐々木 祐典,押切 勉,森田 智慶,本望 修,山下 敏彦.
    • Journal Title

      Precision Medicine

      Volume: 2 Pages: 1032-1035

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 脊髄損傷に対するリハビリテーション医療-実践と挑戦-:脊髄損傷患者に対する自家骨髄間葉系幹細胞移植とリハビリテーション治療.2019

    • Author(s)
      5)森田 智慶,佐々木 祐典,本望 修,山下 敏彦.
    • Journal Title

      The Japanese Journal of Rehabilitation Medicine

      Volume: 56 Pages: 552-554

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Antidepressant activities of escitalopram and blonanserin on prenatal and adolescent combined stress-induced depression model: Possible role of neurotrophic mechanism change in serum and nucleus accumbens.2019

    • Author(s)
      Furuse K, Ukai W, Hashimoto E, Hashiguchi H, Kigawa Y, Ishii T, Tayama M, Deriha K, Shiraishi M, Kawanishi C.
    • Journal Title

      J Affect Disord.

      Volume: 247 Pages: 97-104

    • DOI

      10.1016/j.jad.2019.01.007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of somatic mutations in postmortem human brains by whole genome sequencing and their implications for psychiatric disorders.2018

    • Author(s)
      Nishioka M, Bundo M, Ueda J, Katsuoka F, Sato Y, Kuroki Y, Ishii T, Ukai W, Murayama S, Hashimoto E, Nagasaki M, Yasuda J, Kasai K, Kato T, Iwamoto K.
    • Journal Title

      Psychiatry Clin Neurosci.

      Volume: 72 Issue: 4 Pages: 280-294

    • DOI

      10.1111/pcn.12632

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 深い学びの要 ディープコミュニケーションとは何か:どことどこで会話をしているのか2018

    • Author(s)
      鵜飼渉,辻野華子,杉村政樹,木川昌康,田山真矢,石井貴男,古瀬研吾,廣瀬奨真,橋本恵理,澤田いずみ,山本武志,白鳥正典,河西千秋,相馬仁.
    • Journal Title

      医療人育成センター紀要

      Volume: 9 Pages: 35-43

    • NAID

      120006633026

    • Related Report
      2018 Research-status Report
  • [Presentation] 腎移植後に発生した精神症状に対し薬物療法が著効した2例.2021

    • Author(s)
      小笠原 卓音,田中 俊明,太刀川 公人,橋本 浩平,小林 皇,木川 昌康,河西 千秋,舛森 直哉.
    • Organizer
      第54回日本臨床腎移植学会.
    • Related Report
      2020 Annual Research Report
  • [Presentation] 統合失調症の社会性認知機能障害の脳基盤解析:Glutamate/GABAニューロンバランスメカニズムからの検討.2020

    • Author(s)
      出利葉 健太,鵜飼 渉,Riva Marco,西村 恵美,橋本 恵理,木川 昌康,橋口 華子,古瀬 研吾,田山 真矢,村山 友規,石井 貴男,河西 千秋.
    • Organizer
      日本神経精神薬理学会年会・日本生物学的精神医学会年会・日本精神薬学会総会・学術集会合同年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 胎生期免疫ストレス誘発統合失調症モデルの社会性行動とGABA作動性インターニューロン変化に関する研究.2019

    • Author(s)
      橋本 恵理,鵜飼 渉,西村 恵美,橋口 華子,木川 昌康,田山 真矢,出利葉 健太,古瀬 研吾,石井 貴男,河西 千秋.
    • Organizer
      第115回日本精神神経学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 神経領域における創薬研究の新たな展開: 神経機能の回復をめざして:脳梗塞と脊髄損傷等に対する骨髄間葉系幹細胞の静脈内投与による細胞移植療法.2019

    • Author(s)
      佐々木 祐典,本望 修
    • Organizer
      第37回日本神経治療学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト死後脳の神経細胞におけるLINE-1プロモーターのエピジェネティック修飾状態の検討.2019

    • Author(s)
      渡邊理紗,文東美紀,上田順子,村田唯,石井貴男,鵜飼渉,橋本恵理,笠井清登,清水史郎,加藤忠史,岩本和也.
    • Organizer
      生物学的精神医学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ドパミン調節異常症候群の薬物療法:ミルタザピンが奏効した1例からの考察.2018

    • Author(s)
      荻野裕介,古瀬研吾,佐藤謙太郎,保前英希.
    • Organizer
      精神神経学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Effects of antipsychotics on prenatal immune stress-induced schizophrenia: studies on social behavior and GABAergic interneuron function changes.2018

    • Author(s)
      Ukai W, Tsujino H, Kigawa Y, Tayama M, Deriha K, Furuse K, Nishimura E, Ishii T, Hashimoto E, Kawanishi C.
    • Organizer
      The World Federation of Societies of Biological Psychiatry (WFSBP)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] The Neuroscience of Depression: Features, Diagnosis, and Treatment. Chapter 36, Escitalopram and blonanserin as antidepressant agents linking in neurotrophic mechanisms.2021

    • Author(s)
      Ukai W, Deriha K, Hashimoto E, Kawanishi C.
    • Total Pages
      1166
    • Publisher
      Elsevier
    • ISBN
      9780128180099
    • Related Report
      2020 Annual Research Report
  • [Book] たこつぼ症候群:これまでの歩みと未来へのメッセージ.土橋和文,上嶋健治 編.VI 鑑別すべき病態について ⑤精神疾患およびストレスとたこつぼ症候群.2021

    • Author(s)
      出利葉 健太,鵜飼 渉,橋本 恵理,河西 千秋.
    • Total Pages
      242
    • Publisher
      京誠堂出版
    • ISBN
      9784771905405
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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