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Role of neurotrophin receptor p75 in psychiatric diseases

Research Project

Project/Area Number 20390318
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

KUNUGI Hiroshi  独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第三部, 部長 (40234471)

Co-Investigator(Kenkyū-buntansha) NUMAKAWA Tadahiro  独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第三部, 室長 (40425690)
FUJII Takashi  独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第三部, 科研費研究員 (10450610)
Project Period (FY) 2008 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2010: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2009: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2008: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Keywords遺伝子 / 神経科学 / 脳神経疾患 / 薬理学 / 神経栄養因子
Research Abstract

We have investigated the role of neurotrophins such as brain-derived neurotrophic factor and their receptors in psychiatric disease. In this study, we generated novel transgenic mice that overexpress p75^<NTR> specifically in the forebrain. Transgenic mice were identified based on southern blot analysis. Western blotting and immunohistochemical staining were used to determine the expression pattern of the transgene. We observed the very high levels of p75^<NTR> protein in the hippocampus and cortex lines, but not in cerebellum in these analyses. According to the results of autopsy, the general morphology of brains of adult transgenic mice appeared normal. We have been conducted cooperative research on behavioral analysis with technology and Development Team for Mouse Phenotype Analysis, RIKEN BioResource Center. Our transgenic mice were estimated by light/dark transition, open-field test, home-cage activity test, passive avoidance test, tail suspension test, hot-plate test, tail-flick test. Then, they showed hyper-activity. Furthermore, we reported evidence supporting the association between the Ser205Leu polymorphism of p75^<NTR> and MDD in our original sample and in the meta-analysis.

Report

(6 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report   Self-evaluation Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (36 results)

All 2011 2010 2009 2008 Other

All Journal Article (19 results) (of which Peer Reviewed: 13 results) Presentation (9 results) Book (2 results) Remarks (6 results)

  • [Journal Article] Support for association between the Ser205Leu polymorphism of p75 NTR and major depressive disorder2011

    • Author(s)
      Fujii T, Ota M, Hori H, Sasayama D, Hattori K, Teraishi T, Yamamoto N, Hashikura M, Tatsumi M, Higuchi T, Kunugi H.
    • Journal Title

      J Hum Genet

      Volume: 56 Issue: 11 Pages: 806

    • DOI

      10.1038/jhg.2011.107

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible association of the semaphorin 3D gene (SEMA3D) with schizophrenia.2011

    • Author(s)
      Fujii T, Uchiyama H, Yamamoto N, Hori H, Tatsumi M, Ishikawa M, Arima K, Higuchi T, Kunugi H.
    • Journal Title

      J Psychiatr Res. 45(1)

      Pages: 47-53

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Possible association of the semaphorin 3D gene (SEMA3D) with schizophrenia.2011

    • Author(s)
      Fujii T, et al.
    • Journal Title

      J Psychiatr Res.

      Volume: 45 Pages: 47-53

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression2010

    • Author(s)
      Kunugi H, Hori H, Adachi N, Numakawa T.
    • Journal Title

      Psychiatry Clin Neurosci

      Volume: 64 Issue: 5 Pages: 447

    • DOI

      10.1111/j.1440-1819.2010.02135.x

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sexually dimorphic effect of the Val66Met oolymorphism of BDNF on susceptibility to Alzheimer's disease: New data and meta-analysis2010

    • Author(s)
      Fukumoto N, Fujii T, Combarros O, Kamboh MI, Tsai SJ, Matsushita S, Nacmias B, Comings DE, Arboleda H, Ingelsson M, Hyman BT, Akatsu H, Grupe A, Nishimura AL, Zatz M, Mattila KM, Rinne J, Goto Y, Asada T, Nakamura S, Kunugi H.
    • Journal Title

      Am J Med Genet B Neuropsychiatr Genet

      Volume: 153 Issue: 1 Pages: 235

    • DOI

      10.1002/ajmg.b.30986

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression.2010

    • Author(s)
      Kunugi H, Hori H, Adachi N, Numakawa T.
    • Journal Title

      Psychiatry Clin Neurosci. 64(5)

      Pages: 447-459

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Sexually dimorphic effect of the Val66Met polymorphism of BDNF on susceptibility to Alzheimer's disease : New data and meta-analysis.2010

    • Author(s)
      Fukumoto N, Fujii T, Combarros O, Kamboh MI, Tsai SJ, Matsushita S, Nacmias B, Comings DE, Arboleda H, Ingelsson M, Hyman BT, Akatsu H, Grupe A, Nishimura AL, Zatz M, Mattila KM, Rinne J, Goto Y, Asada T, Nakamura S, Kunugi H.
    • Journal Title

      Am J Med Genet B Neuropsychiatr Genet. 153B(1)

      Pages: 235-242

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression.2010

    • Author(s)
      Kunugi H, et al.
    • Journal Title

      Psychiatry Clin Neurosci.

      Volume: 64 Pages: 447-459

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible interaction between glucocorticoid and BDNF function2010

    • Author(s)
      Numakawa T, Kunugi H.
    • Journal Title

      生化学

      Volume: 82 Pages: 419-422

    • NAID

      10026425972

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BDNF function and intracellular signaling in neurons2010

    • Author(s)
      Numakawa T, et al
    • Journal Title

      Histol Histopathol 25

      Pages: 237-258

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sexually dimorphic effect of the Val66Met polymorphism of BDNF on susceptibility toAlzheimer's disease : New data and meta-analysis2010

    • Author(s)
      Fukumoto N, et al
    • Journal Title

      Am J Med Genet B Neuropsychiatr Genet 153B

      Pages: 235-242

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucocorticoid attenuates brain-derived neurotrophic factor-dependent upregulation of glutamate receptors via the suppression of microRNA-132expression2010

    • Author(s)
      Kawashima H, et al
    • Journal Title

      Neuroscience 165

      Pages: 1301-1311

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p75NTR as a therapeutic target for neuropsychiatric diseases2009

    • Author(s)
      Fujii T, Kunugi H.
    • Journal Title

      Curr Mol Pharmacol

      Volume: 2(1) Pages: 70-6

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/20021447

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Glucocorticoid receptor interaction with TrkB promotes BDNF-triggered PLC-γ signaling for glutamate release via a glutamate transporter2009

    • Author(s)
      Numakawa T, Kumamaru E, Adachi N, Yagasaki Y, Izumi A, Kunugi H.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 106 Issue: 2 Pages: 647

    • DOI

      10.1073/pnas.0800888106

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] p75NTR as a therapeutic target for neuropsychiatric diseases.2009

    • Author(s)
      Fujii T, Kunugi H.
    • Journal Title

      Curr Mol Pharmacol. 2(1)

      Pages: 70-76

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] BDNF is not associated with schizophrenia : data from a Japanese population study and meta-analysis.2009

    • Author(s)
      Kawashima K, Ikeda M, Kishi T, Kitajima T, Yamanouchi Y, Kinoshita Y, Okochi T, Aleksic B, Tomita M, Okada T, Kunugi H, Inada T, Ozaki N, Iwata N.
    • Journal Title

      Schizophr Res. 112(1-3)

      Pages: 72-79

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Glucocorticoid receptor interaction with TrkB promotes BDNF-triggered PLC-gamma signaling for glutamate release via a glutamate transporter.2009

    • Author(s)
      Numakawa T, Kumamaru E, Adachi N, Yagasaki Y, Izumi A, Kunugi H.
    • Journal Title

      Proc Natl Acad Sci U S A. 106(2)

      Pages: 647-652

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Glucocorticoid receptor interaction with TrkB promotes BDNF-triggered PLC-gamma signaling for glutamate release via a glutamate transporter2009

    • Author(s)
      Tadahiro Numakawa, et al.
    • Journal Title

      Proc Natl Acad Sci USA. 106

      Pages: 647-652

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p75NTR as a Therapeutic Target for Neuropsychiatric Diseases2009

    • Author(s)
      Takashi Fujii, et al.
    • Journal Title

      Current Molecular Pharmacology 2

      Pages: 70-76

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 大うつ病性障害におけるp75NTR遺伝子のミスセンス多型Ser205Leuの解析2011

    • Author(s)
      藤井崇
    • Organizer
      第34回日本神経科学会
    • Place of Presentation
      横浜
    • Year and Date
      2011-09-16
    • Related Report
      2011 Final Research Report
  • [Presentation] 大うつ病性障害におけるp75NTR遺伝子のミスセンス多型Ser205Leuの解析2011

    • Author(s)
      Fujii T, et al
    • Organizer
      第34回日本神経科学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2011-09-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] グルココルチコイドと神経栄養因子を鍵分子とした精神疾患研究2010

    • Author(s)
      功刀浩
    • Organizer
      第2回生物学・化学・情報科学融合のための戦略的先進理工学研究基盤の形成(FBT)・超専攻型融合テーマスタディクラスター教育(TSC-PBL)ジョイントシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2010-01-23
    • Related Report
      2011 Final Research Report 2010 Self-evaluation Report
  • [Presentation] 食事・栄養による脳由来神経栄養因子(BDNF)の発現調節とメンタルヘルス2010

    • Author(s)
      功刀浩
    • Organizer
      第13回日本病態栄養学会年次学術集会
    • Place of Presentation
      グランドプリンスホテル京都
    • Year and Date
      2010-01-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] BDNF遺伝子の機能多型Val66Metとアルツハイマー病発症との女性特異的関連2009

    • Author(s)
      藤井崇
    • Organizer
      日本人類遺伝学会第54回大会
    • Place of Presentation
      東京
    • Year and Date
      2009-09-26
    • Related Report
      2011 Final Research Report 2010 Self-evaluation Report
  • [Presentation] BDNF遺伝子の機能多型Val66Metとアルツハイマー病発症との女性特異的関連2009

    • Author(s)
      藤井崇
    • Organizer
      日本人類遺伝学会第54回大会
    • Place of Presentation
      グランドプリンスホテル高輪
    • Year and Date
      2009-09-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] グルココルチコイド受容体およびBDNF受容体の相互作用に制御されるBDNF依存的グルタミン酸放出2009

    • Author(s)
      沼川忠広
    • Organizer
      第52回日本神経化学会大会
    • Place of Presentation
      伊香保温泉ホテル
    • Year and Date
      2009-06-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] Altered expression of BDNF gene and vulnerability to stress in Schizophrenia.2008

    • Author(s)
      Kunugi H
    • Organizer
      XXVI CINP Congress.
    • Place of Presentation
      Munich, Germany.
    • Year and Date
      2008-07-16
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] Altered expression of BDNF gene and vulnerability to stress in Schizophrenia2008

    • Author(s)
      Kunugi H
    • Organizer
      XXVI CINP Congress
    • Place of Presentation
      Munich, Germany
    • Year and Date
      2008-07-16
    • Related Report
      2008 Annual Research Report
  • [Book] うつ病のBDNF仮説.最新うつ病のすべて2010

    • Author(s)
      功刀浩
    • Publisher
      医歯薬出版
    • Related Report
      2011 Final Research Report
  • [Book] 別冊・医学のあゆみ(うつ病のBDNF仮説.最新うつ病のすべて)(樋口輝彦編)2010

    • Author(s)
      功刀浩
    • Publisher
      医歯薬出版,東京
    • Related Report
      2010 Self-evaluation Report
  • [Remarks] 「BDNFのVal66Met多型は女性ではアルツハイマー危険因子、国立精神・神経セが世界16機関からタイピングデータの協力得る(日本人類遺伝学会第54回大会、発表者藤井崇)」日経バイオニュース2009年9月29日報道関連情報

    • URL

      https://bio.nikkeibp.co.jp/article/oc/2006/5641/

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.ncnp.go.jp/nin/guide/r3/index.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.ncnp.go.jp/nin/guide/r3/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks] ホームページ

    • URL

      http://www.ncnp.go.jp/nin/guide/r3/index.html

    • Related Report
      2010 Self-evaluation Report
  • [Remarks]

    • URL

      http://www.ncnp.go.jp/nin/guide/r3/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.ncnp.go.jp/nin/guide/r3/index.html

    • Related Report
      2009 Annual Research Report

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

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