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Molecular mechanisms for the control of monoamine levels in the brain and the etiology of PTSD using serotonin-deficient mice.

Research Project

Project/Area Number 21500305
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionTokyo Institute of Technology

Principal Investigator

ICHINOSE Hiroshi  東京工業大学, 大学院・生命理工学研究科, 教授 (90192492)

Co-Investigator(Kenkyū-buntansha) HIROFUMI Tokuoka  東京工業大学, 大学院・生命理工学研究科, 助教 (10452020)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords臨床神経科学 / 脳神経疾患 / 神経科学 / 医療・福祉 / 蛋白質 / 生理学 / タンパク質
Research Abstract

We first succeeded in generating gene-targeting mice for the dihydropteridine reductase gene. The mice exhibited deficiency in the serotonin contents in the brain and PTSD-like behaviors in a battery of behavioral test. In this study, we explored the molecular mechanism for these abnormalities in the mice. We found that hyperphenylalaninemia in the mice can cause serotonin deficiency in the brain, and that a low-phenylalanine diet deteriorated the serotonin-deficiency in the mice.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (34 results)

All 2013 2012 2011 2010 2009 Other

All Journal Article (20 results) (of which Peer Reviewed: 20 results) Presentation (14 results)

  • [Journal Article] The role of tetrahydrobiopterin and catecholamines in the developmental regulation of tyrosine hydroxylase level in the brain.2013

    • Author(s)
      Homma, D., Katoh, S., Tokuoka, H. & Ichinose, H.
    • Journal Title

      Journal of Neurochemistry

      Volume: (in press) Issue: 1 Pages: 70-81

    • DOI

      10.1111/jnc.12287

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis.2013

    • Author(s)
      Sekiya T, Kashiwagi I, Yoshida R, Fukaya T, et al.
    • Journal Title

      Nat Immunol.

      Volume: 14 Issue: 3 Pages: 230-237

    • DOI

      10.1038/ni.2520

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the dopaminergic system in a murine model of aromatic L-amino acid decarboxylase deficiency2013

    • Author(s)
      Lee, N.-C., Shieh, Y.-D., Chien, Y.-H., Tzen, K.-Y., Yu, I.-S., Chen, P.-W., Hu, M.-H., Hu, M., Muramatsu, S., Ichinose, H., et al.
    • Journal Title

      Neurobiology of disease

      Volume: 52 Pages: 177-90

    • DOI

      10.1016/j.nbd.2012.12.005

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association of monoamine-synthesizing genes with the depression tendency and personality in chronic fatigue syndrome patients2013

    • Author(s)
      Fukuda, S., Horiguchi, M., Yamaguti, K., Nakatomi, Y., Kuratsune, H., Ichinose, H., and Watanabe, Y.
    • Journal Title

      Life Sciences

      Volume: 92 Issue: 3 Pages: 183-18

    • DOI

      10.1016/j.lfs.2012.11.016

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] GTP cyclohydrolase 1 gene haplotypes as predictors of SSRI response in Japanese patients with major depressive disorder2012

    • Author(s)
      Kishi, T., Ichinose, H., Yoshimura, R., Fukuo, Y., Kitajima, T., Inada, T., Kunugi, H., Kato, T., Yoshikawa, T., Ujike, H., et al.
    • Journal Title

      Journal of Affective Disorders

      Volume: 142 Issue: 1-3 Pages: 315

    • DOI

      10.1016/j.jad.2012.05.004

    • URL

      https://pure.teikyo.jp/en/publications/df960119-c92f-4d6a-bc2c-25feadbae8be

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The nitric oxide-cyclic GMP pathway regulates FoxO and alters dopaminergic neuron survival in Drosophila2012

    • Author(s)
      Kanao, T., Sawada, T., Davies, S.-A., Ichinose, H., Hasegawa, K., Takahashi, R., Hattori, N., and Imai, Y
    • Journal Title

      PloS one

      Volume: 7 Issue: 2 Pages: 1-13

    • DOI

      10.1371/journal.pone.0030958

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recovery of neurogenic amines in phenylketonuria mice after liver-targeted gene therapy2012

    • Author(s)
      Yagi, H., Sanechika, S., Ichinose, H., Sumi-Ichinose, C., Mizukami, H., Urabe, M., Ozawa, K., and Kume, A.
    • Journal Title

      Neuroreport

      Volume: 23 Issue: 1 Pages: 30-34

    • DOI

      10.1097/wnr.0b013e32834e3a87

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recovery of neurogenic amines in phenylketonuria mice after liver-targeted gene therapy.2012

    • Author(s)
      Yagi et al.
    • Journal Title

      NeuroReport

      Volume: 23 Pages: 30-34

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Compensatory regulation of dopamine after ablation of the tyrosine hydroxylase gene in the nigrostriatal projection2011

    • Author(s)
      Tokuoka, H., Muramatsu, S., Sumi- Ichinose, C., Sakane, H., Kojima, M., Aso, Y., Nomura, T., Metzger, D., and Ichinose, H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 286 Issue: 50 Pages: 43549-43558

    • DOI

      10.1074/jbc.m111.284729

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells2011

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

      Nature Communications

      Volume: 2 Issue: 1 Pages: 269-269

    • DOI

      10.1038/ncomms1272

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biopterin levels in the cerebrospinal fluid of patients with PARK8 (I2020T)2011

    • Author(s)
      Koshiba, S., Tokuoka, H., Yokoyama, T., Horiuchi, E., Ichinose, H., andHasegawa, K.
    • Journal Title

      Journal of Neural Transmission

      Volume: 118 Issue: 6 Pages: 899-903

    • DOI

      10.1007/s00702-011-0587-8

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Partial biopterin deficiency disturbs postnatal development of the dopaminergic system in the brain2011

    • Author(s)
      Homma, D., Sumi-Ichinose, C., Tokuoka, H., Ikemoto, K., Nomura, T., Kondo, K., Katoh, S., and Ichinose, H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 286 Issue: 2 Pages: 1445-1452

    • DOI

      10.1074/jbc.m110.159426

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Compensatory regulation of dopamine after ablation of the tyrosine hydroxylase gene in the nigrostriatal projection.2011

    • Author(s)
      Tokuoka et al.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 286 Pages: 43549-43558

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Partial biopterin deficiency disturbs postnatal development of the dopaminergic system in the brain.2011

    • Author(s)
      Homma et al.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 286 Pages: 1445-1452

    • Related Report
      2011 Annual Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Advanced research on dopamine signaling to develop drugs for the treatment of mental disorders: regulation of dopaminergic neural transmission by tyrosine hydroxylase protein at nerve terminals2010

    • Author(s)
      Sumi-Ichinose, C., Ichinose, H., Ikemoto, K., Nomura, T., and Kondo, K.
    • Journal Title

      Journal of Pharmacological Science

      Volume: 114 Pages: 17-24

    • NAID

      10029889595

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of dopaminergic neural transmission by tyrosine hydroxylase protein at nerve terminals.2010

    • Author(s)
      Sumi-Ichinose C, et al.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 114 Pages: 17-24

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of tyrosine hydroxylase (TH) gene transcription induced by brain-derived neurotrophic factor (BDNF) and its selective inhibition through Ca2+ signals evoked via the N-methyl-D-aspartate (NMDA) receptor.2010

    • Author(s)
      Fukuchi M, et al.
    • Journal Title

      Brain Research

      Volume: 1366 Pages: 18-26

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accumulation of phosphorylated tyrosine hydroxylase into insoluble protein aggregates by inhibition of an ubiquitin-proteasome system in PC12D cells2009

    • Author(s)
      Kawahata I, et al.
    • Journal Title

      Journal of Neural Transmission

      Volume: 116 Pages: 1571-1578

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of TRK-820, a selective kappa opioid receptor agonist, on rat schizophrenia model.2009

    • Author(s)
      Yoshikawa S, et al.
    • Journal Title

      European Journal of Pharmacology

      Volume: 606 Pages: 102-108

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons.2009

    • Author(s)
      Kadkhodaei B, et al.
    • Journal Title

      Journal of Neuroscience

      Volume: 29 Pages: 15923-15932

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 家族性パーキンソン病PARK8患者の脳脊髄液中ビオプテリン代謝の解析2011

    • Author(s)
      一瀬宏他
    • Organizer
      第9回神経科学研究会
    • Place of Presentation
      東京
    • Year and Date
      2011-11-26
    • Related Report
      2011 Final Research Report
  • [Presentation] モノアミン・ビオプテリン代謝改変マウスを用いたモノアミンニューロンの制御機構と発達変化の解析2011

    • Author(s)
      一瀬宏
    • Organizer
      第64回日本自律神経学会総会
    • Place of Presentation
      秋田市
    • Year and Date
      2011-10-28
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Difference in biopterin metabolism between patients with PARK8 (I2020T) and those with sporadic Parkinson's disease.2011

    • Author(s)
      Hiroshi Ichinose et al.
    • Organizer
      Genomic Epidemiology of Parkinson's Disease (GEO-PD) 2011
    • Place of Presentation
      Illinois, USA
    • Year and Date
      2011-09-20
    • Related Report
      2011 Final Research Report
  • [Presentation] Tetrahydrobiopterin: As a regulator of monoamine signals in the brain2011

    • Author(s)
      Hiroshi Ichinose
    • Organizer
      The 6_th International Conference of Neurons and Brain Diseases
    • Place of Presentation
      富山市
    • Year and Date
      2011-08-04
    • Related Report
      2011 Final Research Report
  • [Presentation] ジヒドロプテリジン還元酵素ノックアウトマウスにおけるセロトニンニューロンの組織化学的解析2011

    • Author(s)
      原慶賢
    • Organizer
      日本ビタミン学会第63回大会
    • Place of Presentation
      広島市
    • Year and Date
      2011-06-05
    • Related Report
      2011 Final Research Report
  • [Presentation] 慢性疲労症候群患者と健常者におけるGTPcyclohydrolaseI遺伝子多型の解析2011

    • Author(s)
      堀口美恵子他
    • Organizer
      第7回日本疲労学会総会学術総会
    • Place of Presentation
      名古屋市
    • Year and Date
      2011-05-21
    • Related Report
      2011 Final Research Report
  • [Presentation] ビオプテリンとドーパミン-線条体におけるドーパミンシグナルの調節機構2010

    • Author(s)
      一瀬宏
    • Organizer
      第25回大脳基底核研究会
    • Place of Presentation
      福島市
    • Year and Date
      2010-07-31
    • Related Report
      2011 Final Research Report
  • [Presentation] ビオプテリンとドーパミン-線条体におけるドーパミンシグナルの調節機構2010

    • Author(s)
      一瀬宏
    • Organizer
      第25回日本大脳基底核研究会
    • Place of Presentation
      福島県福島市
    • Year and Date
      2010-07-31
    • Related Report
      2010 Annual Research Report
  • [Presentation] チロシン水酸化酵素(TH)タンパク質量変化によるドパミン生合成量の調節2009

    • Author(s)
      一瀬宏
    • Organizer
      第32回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2009-09-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] ジヒドロプテリジン還元酵素ノックアウトマウスにおけるセロトニンニューロンの組織化学的解析

    • Author(s)
      原慶賢 他
    • Organizer
      日本ビタミン学会第63回大会
    • Place of Presentation
      広島市(安田女子大学)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 慢性疲労症候群患者と健常者におけるGTP cyclohydrolase I遺伝子多型の解析

    • Author(s)
      堀口美恵子 他
    • Organizer
      第7回日本疲労学会総会学術総会
    • Place of Presentation
      名古屋市(名古屋大学)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 家族性パーキンソン病PARK8患者の脳脊髄液中ビオプテリン代謝の解析

    • Author(s)
      一瀬宏
    • Organizer
      第9回神経科学研究会
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
  • [Presentation] Tetrahydrobiopterin: As a regulator of monoamine signals in the brain.

    • Author(s)
      Hiroshi Ichinose
    • Organizer
      The 6th International Conference of Neurons and Brain Diseases.
    • Place of Presentation
      Toyama (Japan)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Difference in biopterin metabolism between patients with PARK8 (I2020T) and those with sporadic Parkinson’s disease.

    • Author(s)
      Hiroshi Ichinose et al.
    • Organizer
      Genomic Epidemiology of Parkinson’s Disease (GEO-PD) 2011
    • Place of Presentation
      Illinois (USA)
    • Related Report
      2011 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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