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Study on the long-term memory-promoting effect of AMK, a metabolite of melatonin

Research Project

Project/Area Number 20K17520
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionKansai Medical University (2022-2023)
Sophia University (2020-2021)

Principal Investigator

IWASHITA Hikaru  関西医科大学, 医学部, 助教 (90802489)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
KeywordsAMK / Melatonin / 学習 / 記憶 / 抗加齢 / 行動 / 内分泌 / melatonin / メラトニン / 長期記憶 / 加齢 / 老化 / 代謝
Outline of Research at the Start

これまで我々はメラトニンの急性効果による学習記憶の増強作用は、その代謝産物であるAMKが長期記憶誘導作用を持つことによることを報告してきた。しかし、AMKの生理的な作用や役割に関する報告は殆どなく、AMKと記憶の関係について論じた報告はなされていない。長期記憶形成を明確に促進する生体物質の報告はこれまでになく、本研究の目的である急性効果により強力な長期記憶誘導作用を持つAMKの作用機序の解は、学習・記憶の神経機構解明に大いに役立つものであると考えられる。

Outline of Final Research Achievements

Melatonin, which plays an important role in regulating circadian rhythms, has an enhancing effect on learning and memory. In this study, we demonstrated that this potentiation is attributed to the effect of AMK, a melatonin metabolite, and that a single administration of AMK can enhance various types of memory, including working memory, object recognition memory, and spatial memory, using not only young but also old mice. We also showed that endogenous AMK may modulate the formation of learning and memory. These AMK-mediated potentiation of learning and memory may be due to the activation of CREB via activation of ERK and CaMKII.

Academic Significance and Societal Importance of the Research Achievements

日本における高齢者人口の増加は著しく、認知機能低下の予防や改善をもたらす新たなアプローチの開発が持つ重要性は増している。本研究では、メラトニン代謝産物であるAMKが多様な記憶を増強することを示し、老齢個体においても有効であることを確認した。メラトニンは生体内で元々分泌されているホルモンであり、長期にわたる利用や高濃度の利用においても高い安全性が報告されていることから、その代謝産物であるAMKも比較的安全であることが予想され、ヒトへ応用できる可能性は高い。今後さらなる研究を経て、AMKの臨床応用が進めば、認知機能の低下に苦しむ人々のQOL向上に繋がることが期待される。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (9 results)

All 2024 2023 2022 2021

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (3 results)

  • [Journal Article] N1‐Acetyl‐5‐methoxykynuramine, which decreases in the hippocampus with aging, improves long‐term memory via CaMKII/CREB phosphorylation2024

    • Author(s)
      Watanabe Kazuki、Maruyama Yusuke、Iwashita Hikaru、Kato Haruyasu、Hirayama Jun、Hattori Atsuhiko
    • Journal Title

      Journal of Pineal Research

      Volume: 76 Issue: 1

    • DOI

      10.1111/jpi.12934

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of melatonin on phosphorylation of memory-related proteins in the hippocampus and the perirhinal cortex in male mice2023

    • Author(s)
      Sano Masahiro、Iwashita Hikaru、Suzuki Chihiro、Kawaguchi Mari、Chiba Atsuhiko
    • Journal Title

      NeuroReport

      Volume: 34 Issue: 9 Pages: 457-462

    • DOI

      10.1097/wnr.0000000000001911

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diazepam induces retrograde facilitation of object recognition and object location memory in male mice2023

    • Author(s)
      Iwashita H, Sano M, Atsuhiko C
    • Journal Title

      Neuroreport

      Volume: 34(3) Issue: 3 Pages: 137-143

    • DOI

      10.1097/wnr.0000000000001869

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of endogenous and exogenous N-acetyl-5-methoxy kynuramine on object recognition memory in male C3H mice2023

    • Author(s)
      Iwashita H, Sano M, Atsuhiko C
    • Journal Title

      Horm Behav

      Volume: 150 Pages: 105329-105329

    • DOI

      10.1016/j.yhbeh.2023.105329

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] N-acetyl-5-methoxykynuramine enhance object location and working memory performances via modulating CaMKII, ERK and CREB phosphorylation2023

    • Author(s)
      Hikaru Iwashita, Masahiro Sano, Mari Kawaguchi, and Atsuhiko Chiba
    • Journal Title

      NeuroReport

      Volume: 34 Issue: 5 Pages: 299-307

    • DOI

      10.1097/wnr.0000000000001893

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] The melatonin metabolite N1‐acetyl‐5‐methoxykynuramine facilitates long‐term object memory in young and aging mice2021

    • Author(s)
      Iwashita Hikaru、Matsumoto Yukihisa、Maruyama Yusuke、Watanabe Kazuki、Chiba Atsuhiko、Hattori Atsuhiko
    • Journal Title

      Journal of Pineal Research

      Volume: 70 Issue: 1 Pages: 1-11

    • DOI

      10.1111/jpi.12703

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] メラトニンおよびその代謝産物N-acetyl-5-methoxy kynuramine(AMK)による学習記憶能力の増強作用と作用機序の研究2023

    • Author(s)
      岩下洸, 佐野真広, 北田容章, 千葉篤彦
    • Organizer
      第23回日本抗加齢医学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] AMKが制御する学習記憶関連因子と学習記憶能力に与える影響2022

    • Author(s)
      岩下洸、佐野真広、千葉篤彦
    • Organizer
      第48回日本神経内分泌学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 空間記憶に対するメラトニン代謝産物N-acetyl-5-methoxykynuramine (AMK)の長期記憶誘導作用2021

    • Author(s)
      岩下 洸
    • Organizer
      第47回 日本神経内分泌学会学術集会
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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