Molecular basis of cognitive aging caused by perturbed endocannabinoid system

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K17815
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Waseda University
• Principal Investigator: Kataoka Kosuke 早稲田大学, 総合研究機構, 主任研究員 (60822260)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 内在性カンナビノイド系 / 加齢性記憶障害 / ミトコンドリア

Outline of Final Research Achievements

As the aging population rapidly increases in developed countries, I am focusing on the endocannabinoid system (ECS), which is crucial for brain aging, to elucidate the molecular mechanisms of age-related memory impairment. I investigated the cell location-dependent physiological functions of the CB1 receptor, one of the components of the ECS, using SH-SY5Y cells to examine the effects of CB1 receptor activation and inactivation on mitochondrial function. The results suggest that CB1 receptor activity may be involved in mitochondrial membrane potential, morphology, ATP production, ROS production, and cell death (ferroptosis). Furthermore, using other neuronal cell lines and skeletal muscle cell lines, where CB1 receptor expression has been confirmed, the relationship between the CB1 receptor and mitochondrial quality control mechanisms was also clarified.

Free Research Field

神経化学・神経薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究は、加齢性記憶障害の分子機構解明に向けて、内在性カンナビノイド系(ECS)の一つであるCB1受容体に着目し、その細胞内局在依存的な生理機能を明らかにした。CB1受容体の活性が、ミトコンドリアの機能や細胞死に関与することを示唆した成果は、加齢性記憶障害の病態解明に新たな視点を与えるものである。また、CB1受容体の細胞内局在を考慮した創薬デザインにつながる可能性を秘めており、超高齢社会における認知症予防や治療法の開発に寄与することが期待される。