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Investigation on candidate genes involved in pathophysiology of schizophrenia

Research Project

Project/Area Number 16390329
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionTokyo Institute of Psychiatry

Principal Investigator

TATEBAYASHI Yositaka  Tokyo Institute of Psychiatry, Depression Research Project, Project Leader, 東京都精神医学総合研究所, 副参事研究員 (80342814)

Co-Investigator(Kenkyū-buntansha) ITOKAWA Masanari  Tokyo Institute of Psychiatry, Schizophrenia Research Project, Project Leader, 東京都精神医学総合研究所, 副参事研究員 (40332324)
TAKASHIMA Akihiko  RIKEN, BSI, Lab., Alzheimer's disease, Team Leader, 脳科学総合研究センター, チームリーダー (00154774)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2004: ¥6,100,000 (Direct Cost: ¥6,100,000)
Keywordsdepression / dentate gyrus / neurogenesis / senile change / neurofibrillary tangle / tau / Alzheimer's disease / frontotemporal dementia / 神経新生 / モデル動物 / 髄液
Research Abstract

To study the effects of brain senile changes, especially those of neurofibrillary tangles (NFTs), on the depressive symptoms in the elderly, we investigated the transgenic (TG) mice expressing the moderate levels of mutant human tau with R406W mutation in the axons of forebrain neurons postnatally. This mutation causes a type of familial frontotemporal dementia in humans that resembles Alzheimer's disease and is often associated with preclinical depressive symptoms. TG mice exhibited NFTs-like changes in some hippocampal neurons only after they became 19 months old (Tatebayashi et al., 2002, PNAS USA, 99:13896). We analyzed behaviorally 3-21 month-old TG mice and found that these mice showed age-dependent prolongation of the immobile time in the forced swim test when compared to their littermate (Tatebayashi et al., 2004, Neurobil Ag, 25:S249 ; Egashira et al., 2005 Brain Res, 1059:7). This prolongation was associated with the associative memory deficits that appeared at least 7 month- … More old or older male and 15 month-old or older female TG mice. We also found the gene dosage effects in the mood-related behavioral abnormalities. Electrophysiological study further revealed that in TG mice long term potentiation was introduced normally but was associated with the significantly shorter peak decay time than that in their littermates, implying the reduced amounts of neurotransmitters in the presynaptic vesicles, thus possible impairment in the axonal transport in the TG mice. We previously found that physiological tau phosphorylation by GSK-3β may be required for the normal axonal transport (Tatebayashi et al., 2004, J Cell Sci, 117:1653). We therefore examined the effects of R406W mutation on the physiological tau phosphorylation and found that this mutation reduces physiological tau phosphorylation at the PHF-1 site by GSK-3β by affecting the phosphorylation at Ser404 (Tatebayashi et al., 2006, FASEB J, 20:762). Taken together, these data suggest a possibility that R406W tau mutation impairs axonal transport by disrupting the physiological tau phosphorylation, resulting in the age-dependent mood-related behavioral changes in TG mice. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (17 results)

All 2006 2005 2004

All Journal Article (17 results)

  • [Journal Article] c-jun N-terminal kinase hyperphosphorylates R406W tau at the PHF-1 site during mitosis.2006

    • Author(s)
      Tatebayashi Y
    • Journal Title

      The FASEB Journal 20・6

      Pages: 762-764

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Formation of tau inclusions in knock-in mice with familial Alzheimer disease (FAD) mutation of presenilin 1 (PS1).2006

    • Author(s)
      Tanemura K
    • Journal Title

      Journal of Biological Chemistry 281・8

      Pages: 5037-5041

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] c-jun N-terminal kinase yperphosphorylates R406W tau at the PHF-1 site during mitosis.2006

    • Author(s)
      Tatebayashi Y, Planel E, Chui DH, Sato S, Miyasaka T, Sahara N, Murayama M, Kikuchi N, Yoshioka K, Rivka R, Takashima A.
    • Journal Title

      FASEB J. 20(6)

      Pages: 762-764

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Formation of tau inclusions in knock-in mice with familial Alzheimer disease (FAD) mutation of presenilin 1 (PS1).2006

    • Author(s)
      Tanemura K, Chui DH, Fukuda T, Murayama M, Park JM, Akagi T, Tatebayashi Y, Miyasaka T, Kimura T, Hashikawa T, Nakano Y, Kudo T, Takeda M, Takashima A.
    • Journal Title

      J Biol Chem. 281(8)

      Pages: 5037-5041

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] c-jun N-terminal kinase hyperphosphorylates R406W tau at the PHF-1 site during mitosis.2006

    • Author(s)
      Tatebayashi Y
    • Journal Title

      The FASEB Journal Feb.14(Epub ahead of print)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Formation of tau inclusions in knock-in mice with familial Alzheimer disease(FAD) mutation of presenilin 1(PS1).2006

    • Author(s)
      Tanemura K
    • Journal Title

      Journal of Biological Chemistry 281・8

      Pages: 5037-5041

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Altered depression-related behavior and neurochemical changes in serotonergic neurons in mutant R406W human tau transgenic mice.2005

    • Author(s)
      Egashira N
    • Journal Title

      Brain Research 1059・1

      Pages: 7-12

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Altered depression-related behavior and neurochemical changes in serotonergic neurons in mutant R406W human tau transgenic mice.2005

    • Author(s)
      Egashira N, Iwasaki K, Takashima A, Watanabe T, Kawabe H, Matsuda T, Mishima K, Chidori S, Nishimura R, Fujiwara M.
    • Journal Title

      Brain Res. 1059(1)

      Pages: 7-12

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Early behavioral abnormalities in a mouse model of FTDP172004

    • Author(s)
      Tatebayashi Y
    • Journal Title

      Neurobiology of Aging 25

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of tau phosphorylation by glycogen synthase kinase-3beta in the regulation of organelle transport.2004

    • Author(s)
      Tatebayashi Y
    • Journal Title

      Journal of Cell Science 117・9

      Pages: 1653-1663

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Alterations in glucose metabolism induce hypothermia leading to tau hyperphosphorylation through differential inhibition of kinase and phosphatase activities : implications for Alzheimer's disease.2004

    • Author(s)
      Planel E
    • Journal Title

      Journal of Neuroscience 24・10

      Pages: 2401-2411

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Early behavioral abnormalities in a mouse model of FTDP 17.2004

    • Author(s)
      Tatebayashi Y, Tominaga M, Takashima A.
    • Journal Title

      Neurobiol.Aging. 25

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of tau phosphorylation by glycogen synthase kinase-3beta in the regulation of organelle transport.2004

    • Author(s)
      Tatebayashi Y, Haque N, Tung YC, Iqbal K, Grundke-Iqbal I.
    • Journal Title

      J Cell Sci. 117(Pt 9)

      Pages: 1653-1663

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Alterations in glucose metabolism induce hypothermia leading to tau hyperphosphorylation through differential inhibition of kinase and phosphatase activities : implications for Alzheimer's disease.2004

    • Author(s)
      Planel E, Miyasaka T, Launey T, Chui DH, Tanemura K, Sato S, Murayama O, Ishiguro K, Tatebayashi Y, Takashima A.
    • Journal Title

      J Neurosci. 24(10)

      Pages: 2401-2411

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 高齢者のうつと認知障害2004

    • Author(s)
      楯林 義孝
    • Journal Title

      日本神経精神薬理学雑誌 24

      Pages: 273-277

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 老年期うつ病・うつ状態の経過2004

    • Author(s)
      楯林 義孝
    • Journal Title

      老年精神医学雑誌 15・11

      Pages: 1243-1248

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Role of tau phosphorylation by glycogen synthase kinase-3b in the regulation of organelle transport2004

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

      J Cell Sci 117

      Pages: 1653-1663

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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