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Hippocampal neuronal dematuration as a mechanism of action of antidepressant drugs

Research Project

Project/Area Number 22500342
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionNippon Medical School

Principal Investigator

KOBAYSHI Katsunori  日本医科大学, 医学部, 講師 (10322041)

Co-Investigator(Renkei-kenkyūsha) SAKAI Atsushi  日本医科大学, 医学部, 助教 (30386156)
IKEDA Yumiko  日本医科大学, 医学部, 助教 (10386154)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords神経科学 / 脳神経疾患 / 薬理学 / 生理学 / 行動学 / 抗うつ薬 / 海馬 / 神経細胞 / シナプス / 行動解析 / ストレス / 不安
Research Abstract

We examined the effect of the antidepressant fluoxetine on behavior and hippocampal neurons in mice. A high dose of fluoxetine induced behavioral abnormalities including a marked day-to-day fluctuation of activity levels that correlated with functional dematuration of hippocampal neurons. In mice chronically treated with corticosterone that model depressive disorder, neuronal dematuration was facilitated. These results suggest that neuronal dematuration is enhanced in certain pathological states and that the induction of dematuration in the healthy state could contribute to adverse effects of antidepressants.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (24 results)

All 2013 2012 2011 2010

All Journal Article (11 results) (of which Peer Reviewed: 10 results,  Open Access: 1 results) Presentation (13 results)

  • [Journal Article] Corticosterone facilitates fluoxetine-induced neuronal plasticity in the hippocampus.2013

    • Author(s)
      Kobayashi K, Ikeda Y, Asada M, InagakiH, Kawada T, Suzuki H.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 5 Pages: e63662-e63662

    • DOI

      10.1371/journal.pone.0063662

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The immature dentate gyrus represents a shared phenotype of mouse models of epilepsy and psychiatric disease.2013

    • Author(s)
      Shin R, Kobayashi K, Hagihara H, Kogan JH, Miyake S, Tajinda K, Walton NM, Gross AK, Heusner CL, Chen Q, Tamura K, Miyakawa T, Matsumoto M.
    • Journal Title

      Bipolar Disord

      Volume: - Issue: 4 Pages: 405-421

    • DOI

      10.1111/bdi.12064

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synaptosomal-associated protein 25 mutation induces immaturity of the dentate granule cells of adult mice.2013

    • Author(s)
      Ohira K, Kobayashi K, Toyama K, Nakamura HK, Shoji H, Takao K, Takeuchi R, Yamaguchi S, Kataoka M, Otsuka S, Takahashi M, Miyakawa T.
    • Journal Title

      Molecular Brain

      Volume: 6 Issue: 1 Pages: 12-12

    • DOI

      10.1186/1756-6606-6-12

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Deficiency of schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia.2013

    • Author(s)
      Takao K, Kobayashi K, Hagihara H, Ohira K, Shoji H, Hattori S, Koshimizu H, Umemori J, Toyama K, Nakamura HK, Kuroiwa M, Maeda J, Atsuzawa K, Esaki K, Yamaguchi S, Furuya S, Takagi T, Walton NM, Hayashi N, Suzuki H, Higuchi M, Usuda N, Suhara T, Nishi A, Matsumoto M, Ishii S, Miyakawa T.
    • Journal Title

      Neuropsychopharmacology

      Volume: 38(8) Issue: 8 Pages: 1409-25

    • DOI

      10.1038/npp.2013.38

    • Related Report
      2012 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired synaptic clustering of postsynaptic density proteins and altered signal transmission in hippocampal neurons, and disrupted learning behavior in PDZ1 and PDZ2 ligand binding-deficient PSD-95 knockin mice.2012

    • Author(s)
      Nagura H, Ishikawa Y, Kobayashi K, Takao K, Tanaka T, Nishikawa K, Tamura H, Shiosaka S, Suzuki H, Miyakawa T, Fujiyoshi Y, Doi T.
    • Journal Title

      Mol Brain

      Volume: 5 Issue: 1 Pages: 43-43

    • DOI

      10.1186/1756-6606-5-43

    • NAID

      120005323021

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronic fluoxetine selectively upregulates dopamine D1-like receptors in the hippocampus.2012

    • Author(s)
      Kobayashi K, Haneda E, Higuchi M, SuharaT, Suzuki H.
    • Journal Title

      Neuropsychopharmacology

      Volume: 37 Issue: 6 Pages: 1500-1508

    • DOI

      10.1038/npp.2011.335

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SSRIによる海馬神経成熟の逆転2011

    • Author(s)
      小林克典
    • Journal Title

      医学のあゆみ

      Volume: 237 Pages: 793-794

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Journal Article] Correlated alterations in serotonergic and dopaminergic modulations at the hippocampal mossy fiber synapse in mice lacking dysbindin.2011

    • Author(s)
      Kobayashi K, Umeda-Yano S, Yamamori H, Takeda M, Suzuki H, Hashimoto R.
    • Journal Title

      PLoS One

      Volume: 6 Issue: 3 Pages: e18113-e18113

    • DOI

      10.1371/journal.pone.0018113

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine2011

    • Author(s)
      Kobayashi K, Ikeda Y, Suzuki H.
    • Journal Title

      Mol Brain

      Volume: 4 Issue: 1 Pages: 12-12

    • DOI

      10.1186/1756-6606-4-12

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine.2011

    • Author(s)
      Katsunori Kobayashi
    • Journal Title

      Molecular Brain

      Volume: 4

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correlated alterations in serotonergic and dopaminergic modulations at the hippocampal mossy fiber synapse in mice lacking dysbindin.2011

    • Author(s)
      Katsunori Kobayashi
    • Journal Title

      PLoS ONE

      Volume: 6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 抗うつ作用の細胞基盤としての海馬神経脱成熟2013

    • Author(s)
      小林克典
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] 電気けいれん刺激は海馬歯状回顆粒細胞の機能的成熟を逆転させる2012

    • Author(s)
      小林克典
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] 電気けいれん刺激による海馬歯状回の神経成熟マーカー発現変化2012

    • Author(s)
      井本有基
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Final Research Report
  • [Presentation] シナプス伝達および可塑性におけるPSD-95タンパク質PDZ1/2ドメインの役割2012

    • Author(s)
      名倉仁
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Final Research Report
  • [Presentation] 電気けいれん刺激による海馬歯状回神経の成熟状態の変化2012

    • Author(s)
      井本有基
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都
    • Related Report
      2012 Final Research Report
  • [Presentation] Deficiency of Schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia2012

    • Author(s)
      Takao, K.
    • Organizer
      28th CINP World Congress of Neuropsychopharmacology
    • Place of Presentation
      Stockholm, Sweden
    • Related Report
      2012 Final Research Report
  • [Presentation] セロトニン5-HT4受容体欠損マウスにおける恐怖条件付けのメス特異的な亢進2011

    • Author(s)
      小林克典
    • Organizer
      日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2011-09-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] セロトニン5-HT4受容体欠損マウスにおける恐怖条件付けのメス特異的な亢進2011

    • Author(s)
      小林克典
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] Schnurri-2ノックアウトマウスにおける統合失調症に関連した大脳皮質の異常(MicelackingSchnurri-2displayedcorticalabnormalitiesrelatedtoschizophrenia)2011

    • Author(s)
      高雄啓三
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] Deficiency of Schnurri-2 confers schizophrenia-related phenotypes and inflammatory-like phenomenon in the brain.2011

    • Author(s)
      Takao, K.
    • Organizer
      2011KSBNS-MCCS Conference
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2012 Final Research Report
  • [Presentation] Reversal of hippocampal neuronal maturation as a cellularmechanism of antidepressant action2011

    • Author(s)
      Kobayashi K
    • Organizer
      The 6th International Conference ofNeurons and Brain Diseases
    • Place of Presentation
      富山
    • Related Report
      2012 Final Research Report
  • [Presentation] Serotonergic antidepressants reverse neuronal maturation in adult hippocampus.2010

    • Author(s)
      小林克典
    • Organizer
      国際創薬科学技術学会
    • Place of Presentation
      北京国際会議場
    • Year and Date
      2010-10-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 統合失調症脆弱性遺伝子dysbindin欠損マウスにおけるセロトニン、ドパミンによるシナプス修飾の変化2010

    • Author(s)
      小林克典
    • Organizer
      第33回日本神経科学大会
    • Place of Presentation
      神戸
    • Related Report
      2012 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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