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Molecular mechanism of age-related memory impairment improved by melatonin

Research Project

Project/Area Number 16K07434
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Animal physiology/Animal behavior
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Yukihisa Matsumoto  東京医科歯科大学, 教養部, 助教 (60451613)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsメラトニン / 加齢性記憶障害 / 長期記憶 / フタホシコオロギ / AMK / 昆虫 / 神経行動学
Outline of Final Research Achievements

In the present study, I investigated functional mechanisms of melatonin in long-term memory formation and whether melatonin improves age-related memory impairment. The results suggest that AMK, a melatonin metabolite within the brain, is crucial in the long-term memory formation process, and that melatonin/AMK signaling pathway functions downstream of NO-cGMP pathway which has already been reported to be involved in the process. The capability of long-term memory formation in crickets shows daily fluctuation, higher in the night than during the daytime. From the results, melatonin/AMK signaling pathway is suggested to also play a role in this circadian variation. In addition, I demonstrated that AMK improves age-related memory impairment.

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた、「メラトニンの脳内代謝産物が記憶の形成に重要であり、また加齢性記憶障害を改善する」という結果はすべての生物種において初めての報告である。またこれらの現象は代表者らのグループによるマウスを使った実験系でも再現することができた。よって本研究で得られた知見は、ヒトの加齢性記憶障害を改善する新薬の開発にもつながると期待できる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (27 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (3 results)

  • [Journal Article] Development of behavioural automaticity by extended Pavlovian training in an insect2019

    • Author(s)
      Mizunami M, Hirohata S, Sato A, Arai R, Terao K, Sato M, Matsumoto Y.
    • Journal Title

      Proc. Biol. Sci.

      Volume: 286 Issue: 1894 Pages: 21182132-21182132

    • DOI

      10.1098/rspb.2018.2132

    • NAID

      120006727605

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Signaling pathways for long-term memory formation in the cricket2018

    • Author(s)
      Matsumoto Y, Matsumoto CS, Mizunami M.
    • Journal Title

      Front. Psychol.

      Volume: 9 Pages: 1014-1014

    • DOI

      10.3389/fpsyg.2018.01014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of octopamine and dopamine neurons for mediating appetitive and aversive signals in Pavlovian conditioning in crickets2017

    • Author(s)
      M. Mizunami and Y. Matsumoto
    • Journal Title

      Frontier in Physiology

      Volume: 8 Pages: 1027-1027

    • DOI

      10.3389/fphys.2017.01027

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Searching for cognitive processes underlying insect learning2017

    • Author(s)
      M. Mizunami, C. S. Matsumoto and Y. Matsumoto
    • Journal Title

      The Japanese Journal of Animal Pychology

      Volume: 67 Pages: 1-10

    • NAID

      130006894416

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Roles of OA1 octopamine receptor and Dop1 dopamine receptor in mediating appetitive and aversive reinforcement revealed by RNAi studies2016

    • Author(s)
      Awata H., Wakuda R., Ishimaru Y., Matsuoka Y., Terao K., Katata S., Matsumoto Y., Hamanaka Y., Noji S., Mito T., Mizunami M.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1

    • DOI

      10.1038/srep29696

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of NO-cGMP signaling rescues age-related memory impairment in crickets.2016

    • Author(s)
      Y. Matsumoto, C. Sato, T. Takahashi and M. Mizunami
    • Journal Title

      Front. Behav. Neurosci.

      Volume: 10: 166

    • DOI

      10.3389/fnbeh.2016.00166

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effects of caffeine on olfactory learning in crickets.2016

    • Author(s)
      S. Sugimachi, Y. Matsumoto, M. Mizunami and J. Okada
    • Journal Title

      Zool. Sci.

      Volume: 33 Pages: 513-519

    • NAID

      120006987638

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Interaction of inhibitory and facilitatory effects of conditioning trials on long-term memory formation2016

    • Author(s)
      Hosono S, Matsumoto Y, Mizunami M.
    • Journal Title

      Learning & Memory

      Volume: 23 Issue: 12 Pages: 669-678

    • DOI

      10.1101/lm.043513.116

    • NAID

      120006366476

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Olfactory memory in the crickets2019

    • Author(s)
      Y. Matsumoto
    • Organizer
      The 10th International Congress of Comparative Physiology and Biochemistry Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 内因性メラトニン代謝産物N-acetyl-5-methoxykynuramine (AMK)による長期記憶誘導作用2018

    • Author(s)
      岩下洸・松本幸久・丸山雄介・張賢・千葉篤彦・服部淳彦
    • Organizer
      日本抗加齢医学会第18回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] マウスの長期記憶形成に関与する内因性のメラトニン代謝産物N-acetyl-5-methoxykynuramine (AMK)2018

    • Author(s)
      岩下洸・丸山雄介・張賢・松本幸久・千葉篤彦・服部淳彦
    • Organizer
      日本比較内分泌学会第43回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] メラトニン代謝産物N-acetyl-5-methoxykynuramine (AMK)とその類似物質による長期記憶の誘導効果 -コオロギをモデル動物として2017

    • Author(s)
      松本幸久・丸山雄介・松本千尋・影近弘之・増野弘幸・岩下洸・千葉篤彦・服部淳彦
    • Organizer
      日本抗加齢医学会第17回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] メラトニンの脳内代謝産物N-acetyl-5-methoxykynuramine (AMK)による老齢マウスにおける長期記憶誘導作用2017

    • Author(s)
      岩下洸・松本幸久・丸山雄介・千葉篤彦・服部淳彦
    • Organizer
      日本抗加齢医学会第17回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] メラトニンによる長期記憶の誘導効果は投与時刻により異なる―コオロギにおいて2017

    • Author(s)
      佐藤紀之・松本幸久・服部淳彦
    • Organizer
      日本動物学会第88回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 記憶力が低下した加齢マウスにおけるメラトニン脳内代謝産物の長期記憶誘導作用2017

    • Author(s)
      岩下洸・松本幸久・丸山雄介・千葉篤彦・服部淳彦
    • Organizer
      日本動物学会第88回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] コオロギにおける長期記憶形成能の概日変化とメラトニン及びその脳内代謝産物の長期記憶誘導効果2017

    • Author(s)
      佐藤紀之・松本幸久・丸山雄介・服部淳彦
    • Organizer
      第24回日本時間生物学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] コオロギの長期記憶形成能の日内および概日変化と昼夜で異なるメラトニン脳内代謝産物の長期記憶誘導効果2017

    • Author(s)
      佐藤紀之・松本幸久・丸山雄介・服部淳彦
    • Organizer
      日本比較内分泌学会第42回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] メラトニン産生能を持つマウスにおけるメラトニンの脳内代謝産物N-acetyl-5-methoxykynuramine (AMK)の長期記憶誘導作用2017

    • Author(s)
      岩下洸・松本幸久・丸山雄介・張賢・千葉篤彦・服部淳彦
    • Organizer
      日本比較内分泌学会第42回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Prediction error theory in insects; blocking experiment and pharmacological evaluation.2017

    • Author(s)
      K. Terao, Y. Matsumoto, M. Mizunami
    • Organizer
      The 44th Naito Conference: Decision Making in the Brain―Motivation, Prediction, and Learning
    • Related Report
      2017 Research-status Report
  • [Presentation] メラトニンの脳内代謝産物であるN-acetyl-5-methoxykynuramine (AMK)はコオロギの長期記憶形成に重要である2016

    • Author(s)
      松本幸久・丸山雄介・松本‐佐藤千尋・岩下洸・千葉篤彦・服部淳彦
    • Organizer
      比較内分泌学会第41回大会
    • Place of Presentation
      北里大学(神奈川県・相模原市)
    • Year and Date
      2016-12-09
    • Related Report
      2016 Research-status Report
  • [Presentation] メラトニンの脳内代謝産物であるN-acetyl-5-methoxykynuramine (AMK)のマウスにおける長期記憶誘導作用2016

    • Author(s)
      岩下洸・松本幸久・丸山雄介・千葉篤彦・服部淳彦
    • Organizer
      比較内分泌学会第41回大会
    • Place of Presentation
      北里大学(神奈川県・相模原市)
    • Year and Date
      2016-12-09
    • Related Report
      2016 Research-status Report
  • [Presentation] Melatonin metabolites rescue age-related memory impairment in the cricket Gryllus bimaculatus2016

    • Author(s)
      松本幸久・丸山雄介・松本‐佐藤千尋・岩下洸・千葉篤彦・服部淳彦
    • Organizer
      The 22th International Congress of Zoology
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県・宜野湾市)
    • Year and Date
      2016-11-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] メラトニンには単回投与でも長期記憶を誘導する効果がある -コオロギをモデル動物として2016

    • Author(s)
      松本幸久・丸山雄介・松本‐佐藤千尋・岩下洸・千葉篤彦・服部淳彦
    • Organizer
      日本抗加齢医学会第16回大会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-06-10
    • Related Report
      2016 Research-status Report
  • [Presentation] メラトニンには単回投与でも長期記憶を誘導する効果がある-マウスを用いて2016

    • Author(s)
      岩下洸・松本幸久・丸山雄介・服部淳彦・千葉篤彦
    • Organizer
      日本抗加齢医学会第16回大会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-06-10
    • Related Report
      2016 Research-status Report
  • [Book] Crickets as a model organism: development, regeneration and behavior. Chapter 9, Learning and memory.2017

    • Author(s)
      M. Mizunami and Y. Matsumoto
    • Total Pages
      12
    • Publisher
      Springer
    • ISBN
      4431564764
    • Related Report
      2017 Research-status Report
  • [Book] Crickets as a model organism: development, regeneration and behavior. Chapter 16, Reproductive behavior and physiology in the cricket Gryllus bimaculatus.2017

    • Author(s)
      M. Sakai, M. Kumashiro, Y. Matsumoto, M. Ureshi and T. Otsubo
    • Total Pages
      25
    • Publisher
      Springer
    • ISBN
      4431564764
    • Related Report
      2017 Research-status Report
  • [Book] Crickets as a model organism: development, regeneration and behavior. Chapter 17, Protocols for olfactory conditioning.2017

    • Author(s)
      Y. Matsumoto, C. S. Matsumoto and M. Mizunami
    • Total Pages
      12
    • Publisher
      Springer
    • ISBN
      4431564764
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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