Elucidation of a mechanism of developing depression in colitis: association with brain-gut AMPK and development of novel therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15351
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: International University of Health and Welfare
• Principal Investigator: Takahashi Kohei 国際医療福祉大学, 薬学部, 助教 (90846411)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 脳腸相関 / Resveratrol / AMPK / Autophagy / 神経新生 / 神経炎症 / 潰瘍性大腸炎 / ミクログリア分極

Outline of Final Research Achievements

The purpose of this study is to determine the role of AMP-activated protein kinase (AMPK) in the brain and gut in animal models of ulcerative colitis (UC), and to establish novel strategies for the prevention and treatment of UC and co-occurring depression. Our results indicate that the development of UC and co-occurring depression is significantly affected by decreased brain-gut AMPK activity, while AMPK activation in the hippocampus and intestine is important in the treatment of UC symptoms and co-occurring depression.
Therefore, we suggest that the brain-gut AMPK signaling pathways are closely involved in the development of UC-like symptoms and depression-like behavior in animal models of UC, and may be a common target for investigating new therapeutic strategies for UC patients with depression.

Free Research Field

精神神経薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果より、うつ様行動を併発する潰瘍性大腸炎モデルであるデキストラン硫酸ナトリウム処置マウスの海馬並びに直腸においてAMPKシグナル経路の異常が認められ、これらの変化はAMPK活性化剤であるresveratrolの経口投与によって潰瘍性大腸炎様所見並びにうつ様行動と共に改善することを明らかにした。これは潰瘍性大腸炎並びにうつ病の両方に脳腸内AMPKシグナル経路が密接に関与しており、うつ病を併発した潰瘍性大腸炎患者に対する新たな治療法を考究する上での共通標的になり得ることを示唆している。脳腸AMPKに焦点をおいた研究成果はこれまでに報告がなく、学術的並びに社会的に意義のある点だと考える。