Molecular and neural mechanism of age-related memory impairment improved by melatonin metabolic product AMK

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K06759
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Matsumoto Yukihisa 東京医科歯科大学, 統合教育機構, 助教 (60451613)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: AMK / メラトニン / 加齢性記憶障害 / 長期記憶 / フタホシコオロギ / 嗅覚学習

Outline of Final Research Achievements

In the present study, I investigated the functional mechanisms of AMK, a melatonin metabolite, in long-term memory formation in crickets (Gryllus bimaculatus) by behavioral-pharmacological experiments and primary tissue culture. The results suggest that within the long-term memory formation process, the melatonin/AMK signaling pathway functions downstream of the NMDA pathway and insulin pathway, rather than activation of neurons by glycometabolic regulation. Moreover, the use of LC-MS/MS revealed that the amounts of melatonin-related substances in the brain of aged crickets were significantly less compared to those in young adult crickets. The results obtained by RNA-sequencing indicated that expression levels of various memory-related genes in the brain decreased in aged crickets compared to young adult crickets.

Free Research Field

神経行動学

Academic Significance and Societal Importance of the Research Achievements

本研究より、メラトニン/AMKシグナル系がコオロギの長期記憶の形成機構において様々なシグナル伝達経路の下流で働いていることや、加齢に伴い脳内のメラトニン関連物質量が減少することがわかった。これらの知見は、加齢に伴う記憶力低下を改善する薬の開発につながることが期待できる。