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Genetic Dissection of Age-related Memory Impairment

Research Project

Project/Area Number 16300107
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionTokyo Metropolitan Organization for Medical Research

Principal Investigator

SAITOE Minoru  Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Project Leader, 東京都神経科学総合研究所, 副参事研究員 (50261839)

Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2006: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2005: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2004: ¥4,800,000 (Direct Cost: ¥4,800,000)
KeywordsLearning and Memory / PKA / Aging / Mutant / Molecular Mechanism / 遺伝子 / ショウジョウバエ / 学主記憶
Research Abstract

Although it is widely known that aging is associated with memory loss, the specific molecular mechanisms that contribute to age-related memory impairment (AMI) are unknown, because of a lack of AMI-specific mutants. Previously, we determined that Drosophila aging specifically impairs memory phase depending on amnesiac (amn), gene encoding putative neuropeptides, and hypothesized that signaling downstream of amn leads to AMI. In this current project, we extend this work by screening for mutants with altered AMI onset and identifying that heterozygous mutations in DC0, the gene encoding the catalytic subunit of PKA, delay AMI more than two fold without affecting memory at young ages. Furthermore, our identified DC0 mutants do not show any increases in longevity, demonstrating that AMI can be dissociated from organismal aging. Given the identification of DC0, we demonstrate that PKA activity in the mushroom bodies (MBs), structures important in memory formation, causes AMI and AMI onset can be controlled by altering cAMP/PKA signaling activity in the MBs. Notably, putative neuropeptides encoded by amn are proposed to regulate cAMP level, and DPM cells expressing amn innervate MBs. In addition, amn mutants do not show further memory decay upon aging. We show here that both amn-dependent memory and AMI are restored in amn ; DC0/+ double mutants. These results suggest that cAMP/PKA signaling in the MBs is a downstream of amn and leads to AMI upon aging.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (27 results)

All 2007 2006 2005 2004

All Journal Article (23 results) Book (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] The Drosophila DC0 mutation suppresses age-related memory impairment without affecting lifespan.2007

    • Author(s)
      Yamazaki, D
    • Journal Title

      Nature Neurosci 10

      Pages: 478-484

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases.2007

    • Author(s)
      Qi ML
    • Journal Title

      Nat Cell Biol 9

      Pages: 402-414

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The Drosophila DCO mutation suppresses age-related memory impairment without affecting lifespan.2007

    • Author(s)
      Yamazaki D
    • Journal Title

      Nat Neurosci 10

      Pages: 478-484

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression of human PQBP-1 in Drosophila impairs long-term memory and induces abnormal courtship.2006

    • Author(s)
      Yoshimura, N
    • Journal Title

      FEBS Lett 580

      Pages: 2335-2340

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73.2006

    • Author(s)
      Hoshino, M
    • Journal Title

      J Cell Biol 172

      Pages: 589-604

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Expression of human PQBP-1 in Drosophila impairs long-term memory and induces abnormal courtship.2006

    • Author(s)
      Yoshimura N
    • Journal Title

      FEBS Lett 580

      Pages: 2335-2340

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73.2006

    • Author(s)
      Hoshino M
    • Journal Title

      J Cell Biol 172

      Pages: 589-604

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73.2006

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

      J.Cell Biol. 172

      Pages: 589-604

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases.2005

    • Author(s)
      Qi, ML
    • Journal Title

      Nature Cell Biol 9

      Pages: 402-414

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Drosophila as a novel animal model for studying the genetics of age-related memory impairment.2005

    • Author(s)
      Saitoe, M
    • Journal Title

      Rev Neurosci 16

      Pages: 137-149

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] NMDA receptors mediate olfactory learning and memory in Drosophila.2005

    • Author(s)
      Xia, S
    • Journal Title

      Current Biology 15

      Pages: 603-615

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Can flies shed light on our own age-related memory impairment?2005

    • Author(s)
      Xia, S
    • Journal Title

      Ageing Res Rev 4

      Pages: 83-101

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Drosophila as a novel animal model for studying the genetics of age-related memory impairment.2005

    • Author(s)
      Saitoe M
    • Journal Title

      Rev Neurosci 16

      Pages: 137-149

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] NM DA receptors mediate olfactory learning and memory in Drosophila.2005

    • Author(s)
      Xia S
    • Journal Title

      Current Biology 15

      Pages: 603-615

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Can flies shed light on our own an-related memory impairment?2005

    • Author(s)
      Horiuchi J
    • Journal Title

      Ageing Res Rev 4

      Pages: 83-101

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] NMDA receptors mediate olfactory learning and memory in Drosophila.2005

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

      Current Biology 15

      Pages: 603-615

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Drosophila as a novel animal model for studying the genetics of age-related memory impairment.2005

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

      Rev.Neurosci. 16

      Pages: 137-149

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Can flies shed light on our own age-related memory impairment?2005

    • Author(s)
      Horiuchi, J. et al.
    • Journal Title

      Ageing Res Rev 4

      Pages: 83-101

    • Related Report
      2005 Annual Research Report
  • [Journal Article] NMDA receptors mediate olfactory learning and memory in Drosophila.2005

    • Author(s)
      Xia S*, Miyashita T*, Fu T-G*, Lin W-Y, Wu C-L, Pyzocha L, Lin I-R, Saitoe M, Tully T, Chiano A-S.
    • Journal Title

      Current Biology (発表予定)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Drosophila as a novel animal model for studying the genetics of age-related memory impairment2005

    • Author(s)
      Saitoe M, Tamura T, Ito N, Horiuchi J
    • Journal Title

      Rev Neurosci (発表予定)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Can flies shed light on our own age-related memory impairment?2005

    • Author(s)
      Horiuchi J, Saitoe M
    • Journal Title

      Ageing Res Rev 4

      Pages: 83-101

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of the memory component that decays with age in drosophila.2004

    • Author(s)
      Saitoe M, Tamura T, Horiuchi J, Ito N
    • Journal Title

      Jpn J Neuropsychopharmacol 24

      Pages: 231-237

    • NAID

      10015423438

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 加齢により障害される記憶過程とその遺伝子経路の同定2004

    • Author(s)
      齊藤 実
    • Journal Title

      バイオインダストリー 21

      Pages: 27-35

    • Related Report
      2004 Annual Research Report
  • [Book] Sourcebook of model organisms in biomedical research2007

    • Author(s)
      Horiuchi J
    • Publisher
      Humana Press(in press)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Book] ブレインサイエンスレヴュー20042004

    • Author(s)
      齊藤 実
    • Total Pages
      15
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 加齢性記憶障害作用を有するプロテインキナーゼAと、その標的タンパク同定方法2005

    • Inventor(s)
      齊藤 実
    • Industrial Property Rights Holder
      (財)東京都医学研究機構
    • Filing Date
      2005
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 抗加齢性記憶障害作用のあるメラトニンとその誘導体の探索方法2005

    • Inventor(s)
      齊藤実, 宮下知之, 服部淳彦
    • Industrial Property Rights Holder
      (財)東京都医学研究機構, (国)東京医科歯科大学
    • Industrial Property Number
      2005-342946
    • Filing Date
      2005
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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

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