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Elucidation of pathophysiology of refractory depression and development of newer treatment based on the disturbance of spine dynamics

Research Project

Project/Area Number 20591368
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionHiroshima University

Principal Investigator

MORINOBU Shigeru  Hiroshima University, 大学院・医歯薬学総合研究科, 准教授 (30191042)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords難治性うつ病 / 脳由来神経栄養因子 / 樹状突起スパイン / マイクロRNA / 海馬 / 母子分離 / 学習性無力 / trkB受容体 / BDNF / MeCP2 / miR-132 / miR-30a / miR-141 / miR-200a / IMK-1 / microRNA / スパイン / うつ病 / LIMK-1
Research Abstract

The present study was undertaken to examine whether the decreased synaptic density through the spine abnormality in the hippocampus is involved in the pathophysiology of refractory depression. We developed a rat model of refractory depression using neonatal isolation and learned helplessness. The principal findings of this study were that 1) the spine length of dendritic spines was longer in the hippocampus of the model rats without any changes in spine density, 2) the immunoreactivity of brain-derived neurotrophic factor (BDNF) was decreased, 3) the levels of microRNA (miR)-132 were decreased, 4) the levels of miR-134 were not affected, 5) the immunoreactivity of TrkB was decreased. These findings suggested that the spine abnormality due to the decreased BDNF-TrkB signal in the hippocampus may be involved in the pathophysiology of refractory depression, with less contribution by downregulation of BDNF through miR regulation from the 3' region of the BDNF gene.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (25 results)

All 2011 2010 2009 2008 Other

All Journal Article (11 results) (of which Peer Reviewed: 8 results) Presentation (11 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Enhanced hippocampal BDNF/TrkB signaling in response to fear conditioning in an animal model of posttraumatic stress disorder.2011

    • Author(s)
      Takei Shiro, Morinobu Shigeru, Yamamoto Shigeto, Fuchikami Manabu, Matsumoto Tomoya, Yamawaki Shigeto
    • Journal Title

      J Psychiatric Res 45

      Pages: 460-468

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic regulation of BDNF gene in response to stress.2010

    • Author(s)
      Fuchikami Manabu, Yamamoto Shigeto, Morinobu Shigeru, Takei Shiro, Yamawaki Shigeto
    • Journal Title

      Psychiatry Investigation 7

      Pages: 251-256

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Alteration in the hippocampal glycinergic system in an animal model of posttraumatic stress disorder.2010

    • Author(s)
      Yamamoto Shigeto, Morinobu Shigeru, Iwamoto Yasuyuki, Ueda Yuto, Takei Shiro, Fujita Yosuke, Yamawaki Shigeto
    • Journal Title

      J Psychiatric Res 44

      Pages: 1069-1074

    • NAID

      120002753738

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] ストレスとうつ病動物モデル2010

    • Author(s)
      森信繁、高橋輝道、山本茂人
    • Journal Title

      別冊・医学のあゆみ

      Pages: 190-195

    • Related Report
      2010 Final Research Report
  • [Journal Article] Epigenetic regulation of BDNF gene in response to stress2010

    • Author(s)
      Fuchimaki M
    • Journal Title

      Psychiatry Investigation

      Volume: 7 Pages: 251-256

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] うつ病の新たなメカニズム-エピジェネティクス-2010

    • Author(s)
      森信繁
    • Journal Title

      精神神経学雑誌

      Volume: 112 Pages: 986-991

    • NAID

      10028059807

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Maternal postpartum learned helplessness (LH) affects maternal care by dams and responses to the LH test in adolescent offspring.2009

    • Author(s)
      Kurata Akiko, Morinobu Shigeru, Fuchikami Manabu, Yamamoto Shigeto, Yamawaki Shigeto
    • Journal Title

      Horm Behav 56

      Pages: 112-120

    • NAID

      120001700471

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Single immobilization stress differentially alters the expression profile of transcripts of the brain-derived neurotrophic factor (BDNF) gene and histone acetylation at its promoters in the rat hippocampus.2009

    • Author(s)
      Fuchikami M, Morinobu S, Kurata A, Yamamoto S, Yamawaki S
    • Journal Title

      Int J Neuropsychopharmacol 12

      Pages: 73-82

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Maternal postpartum leaned helplessness (LH) affects maternal care by dans and respomses to the LH test in adolescent offspring2009

    • Author(s)
      Kurata A
    • Journal Title

      Hormones and Behavior 56

      Pages: 112-120

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 栄養因子・成長因子とシナプス可塑性からみたうつ病の病態メカニズム2009

    • Author(s)
      森信繁
    • Journal Title

      精神神経学誌 111

      Pages: 687-691

    • NAID

      10026307158

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Prior neonatal isolation reduces induction of NGF mRNA and decreases GDNF mRNA in the hippocampus of juvenile and adult rodents subjected to immobilization stress.2008

    • Author(s)
      Kawano K
    • Journal Title

      Synapse 62

      Pages: 259-267

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Electroconvulsive seizure induced tissue-plasminogen activator (t-PA) expression in rat hippocampus.2010

    • Author(s)
      Segawa Masahiro, Fuchikami Manabu, Matsumoto Tomoya, Morinobu Shigeru, Yamawaki Shigeto
    • Organizer
      Neuro2010
    • Place of Presentation
      San Diego, U.S.A.
    • Related Report
      2010 Final Research Report
  • [Presentation] The effect of the histone deacetylase inhibitor Suberoylanilide hydroximic acid (SAHA) on extinction of conditioned fear.2010

    • Author(s)
      Fujita Yosuke, Morinobu Shigeru, Takei Shiro, Yamamoto Shigeto, Yamawaki Shigeto
    • Organizer
      Neuro2010
    • Place of Presentation
      San Diego, U.S.A.
    • Related Report
      2010 Final Research Report
  • [Presentation] 養育環境の修飾によるうつ病動物モデル作成の可能性について2010

    • Author(s)
      森信繁
    • Organizer
      第32回日本生物学的精神医学会
    • Place of Presentation
      北九州
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Enhanced transcription of the BDNF gene and histone acetylation at its promoters are involved in fear memory consolidation in an animal model of PTSD2010

    • Author(s)
      Takei shiro, Morinobu Shigeru, Yamamoto Shigeto, Fuchikami Manabu, Yamawaki Shigeto
    • Organizer
      CINP2010
    • Place of Presentation
      Hong Kong, China
    • Related Report
      2010 Final Research Report
  • [Presentation] うつ病発症の新たなメカニズム-エピジェネティクス-2010

    • Author(s)
      森信繁
    • Organizer
      第106回日本精神神経学会
    • Place of Presentation
      広島
    • Related Report
      2010 Final Research Report
  • [Presentation] Neonatal isolation as an animal model of vulnerability for depression2009

    • Author(s)
      Morinobu S
    • Organizer
      32th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      名古屋
    • Year and Date
      2009-09-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] Enhanced transcription of the BDNF gene and histone acetylation at its promoters are involved in fear memory consolidation in an animal model of PTSD2009

    • Author(s)
      Morinobu Shigeru, Takei Shiro, Yamamoto Shigeto, Fuchikami Manabu, Yamawaki Shigeto
    • Organizer
      Neuro2009
    • Place of Presentation
      Chicago, U.S.A.
    • Related Report
      2010 Final Research Report
  • [Presentation] 産後早期の母ラットにおける学習性無力が養育行動及び仔のストレス脆弱性に与える影響2009

    • Author(s)
      倉田明子、森信繁、淵上学、山本茂人、松木文、山脇成人
    • Organizer
      第31回日本生物学的精神医学会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] The influence of learned helplessnss (LH) in dams dirung early postpartum period on their maternal care and the response to LH test in their adolscent offspring.2008

    • Author(s)
      倉田明子, 森信繁, 淵上学, 山本茂人, 山脇成人
    • Organizer
      Neuro2008
    • Place of Presentation
      Washington D.C., U.S.A.
    • Related Report
      2010 Final Research Report
  • [Presentation] うつ病発症感受性と養育環境2008

    • Author(s)
      森信繁、倉田明子、淵上学、松木文、土岐茂、山脇成人
    • Organizer
      第49回日本心身医学会総会
    • Place of Presentation
      札幌
    • Related Report
      2010 Final Research Report
  • [Presentation] 栄養因子・成長因子とシナプス可塑性からみたうつ病の病態メカニズム2008

    • Author(s)
      森信繁
    • Organizer
      第104回日本精神神経学会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Book] こころの医学事典(樋口輝彦、野村総一郎編)2010

    • Author(s)
      森信繁
    • Publisher
      日本評論社
    • Related Report
      2010 Final Research Report
  • [Book] 脳とこころのプライマリケア1うつと不安(シナジー、下田和孝編)2010

    • Author(s)
      森信繁
    • Related Report
      2010 Final Research Report
  • [Remarks] 特に該当せず

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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