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Potential involvement of the mitochondrial unfolded protein response in depressive-like symptoms in mice

Research Project

Project/Area Number 25830054
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

KAMBE Yuki  鹿児島大学, 医歯(薬)学総合研究科, 助教 (60549913)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsミトコンドリア / 新規創薬ターゲット / うつ病 / 変性タンパク質ストレス / ミトコンドリア障害 / 変性タンパク質応答 / ドラッグターゲット / マウスモデル / 活性酸素
Outline of Final Research Achievements

Many evidences strongly suggest that a mitochondrial deficit is implicated in major depression. A mitochondrial deficit leads to mitochondrial stress responses, including the mitochondrial unfolded protein response (UPRmt), which is associated with certain brain disorders such as spastic paraplegia and Parkinson’s disease. However, there is no evidence regarding the relationship between depressive disorder and UPRmt. Mice treated with chronic restraint stress showed significant depressive-like behaviors in the tail suspension and forced swim tests, decreased oxygen consumption rate, and increased levels of molecules associated with UPRmt, such as Hspa9, Hspd1, Ubl5, Abcb10, and ClpP. All of the UPRmt-related molecules were significantly correlated with depressive-like behavior in the forced swim test. Thus, the present study is the first to reveal a relationship between the UPRmt and depressive disorder, suggesting that the UPRmt is a potential drug target for depressive disorders.

Report

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

    (16 results)

All 2015 2014 2013 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Invited: 1 results) Remarks (4 results)

  • [Journal Article] Potential involvement of the mitochondrial unfolded protein response in depressive-like symptoms in mice2015

    • Author(s)
      Kambe, Y, Miyata, A
    • Journal Title

      Neurosci Lett

      Volume: 588 Pages: 166-171

    • DOI

      10.1016/j.neulet.2015.01.006

    • NAID

      130007812003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] C-type natriuretic peptide modulates permeability of the blood-brain barrier2014

    • Author(s)
      M. Bohara, Y. Kambe, T. Nagayama, H. Tokimura, K. Arita, and A. Miyata
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: 34 Issue: 4 Pages: 589-596

    • DOI

      10.1038/jcbfm.2013.234

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) gene is suppressed by transglutaminase 2 activation.2013

    • Author(s)
      Miura, A., Kambe, Y., Inoue, K., Tatsukawa, H., Kurihara, T., Griffin, M., Kojima, S. & Miyata, A.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 288 Issue: 45 Pages: 32720-32730

    • DOI

      10.1074/jbc.m113.452706

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Activation of glycogen metabolism by pituitary adenylate cyclase-activating polypeptide in cultured astrocyte2015

    • Author(s)
      神戸 悠輝、中島 優、新谷 紀人、橋本 均、宮田 篤郎
    • Organizer
      第88回 日本薬理学会年会
    • Place of Presentation
      名古屋 (名古屋国際会議場)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Spinal PACAP-specific receptor activation induces long-lasting mechanical allodynia through the activation of astrocytes2015

    • Author(s)
      用皆 正文、栗原 崇、神戸 悠輝、高崎 一朗、宮田 篤郎
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋 (名古屋国際会議場)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 下垂体アデニル酸シクラーゼ活性化ポリペプチドによる脳内グリコーゲン代謝の活性化 〜培 養アストロサイトを用いた研究〜2014

    • Author(s)
      神戸悠輝, 宮田篤郎
    • Organizer
      第 67 回 日本薬理学会西南部会
    • Place of Presentation
      小倉 (産業医科大学)
    • Year and Date
      2014-11-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] 下垂体腺腫細胞 GH3 のプロラクチンおよび成長ホルモン分泌に及ぼすリゾホスファチジルセリ ンの効果2014

    • Author(s)
      井上和彦、竹ノ内里奈、國師恵美子、大和麻耶、神戸悠輝、宮田篤郎
    • Organizer
      第 67 回 日本薬理学会西南部会
    • Place of Presentation
      小倉 (産業医科大学)
    • Year and Date
      2014-11-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Implication of Mitochondria in PACAP signaling :modulation of energy metabolism in brain2014

    • Author(s)
      Atsuro Miyata and Yuki Kambe
    • Organizer
      20th International Symposium on Regulatory Peptides
    • Place of Presentation
      京都 (京都ガーデンパレス)
    • Year and Date
      2014-09-07 – 2014-09-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] PACAPによる神経突起伸展促進作用におけるミトコンドリアの寄与2013

    • Author(s)
      神戸悠輝,宮田篤郎
    • Organizer
      第15回ブレインサイエンス研究会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Presentation] C型ナトリウム利尿ペプチドによる血液脳関門透過性の調節2013

    • Author(s)
      神戸悠輝,Manoj Bohara,栗原崇,永山哲也,有田和徳,宮田篤郎
    • Organizer
      第31回 内分泌代謝学サマーセミナー
    • Place of Presentation
      湯布院
    • Related Report
      2013 Research-status Report
  • [Presentation] C型ナトリウム利尿ペプチドによる血液脳関門透過性の調節2013

    • Author(s)
      神戸悠輝,Manoj Bohara,栗原崇,永山哲也,有田和徳,宮田篤郎
    • Organizer
      第4回 鹿児島神経科学研究会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Research-status Report
  • [Presentation] C-type natriuretic peptide modulates permeability of the blood-brain barrier.2013

    • Author(s)
      M. BOHARA; Y. KAMBE; T. KURIHARA; T. NAGAYAMA; H. TOKIMURA; K. ARITA; A. MIYATA.
    • Organizer
      Neuroscience 2013
    • Place of Presentation
      San Diego
    • Related Report
      2013 Research-status Report
  • [Remarks] 生体情報薬理学のホームページ

    • URL

      http://www.kufm.kagoshima-u.ac.jp/~pharmaco/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 神戸 悠輝の研究概要

    • URL

      http://www.kufm.kagoshima-u.ac.jp/~pharmaco/ukikambe.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 鹿児島大学研究者総覧 - 神戸 悠輝 -

    • URL

      http://kuris.cc.kagoshima-u.ac.jp/512228.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 研究業績 - 生体情報薬理学

    • URL

      http://www.kufm.kagoshima-u.ac.jp/~pharmaco/achievement.html

    • Related Report
      2013 Research-status Report

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

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