Research on the role of Nrf2 in cognitive dysfunction induced by exposure to inorganic arsenic

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03185
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: TAKATA Ayako 聖マリアンナ医科大学, 医学部, 教授 (30321897)
• Co-Investigator(Kenkyū-buntansha): 山内 博 聖マリアンナ医科大学, 医学部, 教授 (90081661) ; 人見 敏明 聖マリアンナ医科大学, 医学部, 准教授 (90405275)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ヒ素 / 認知機能障害 / 血液脳関門 / タイトジャンクション傷害 / Nrf2 / メチル化 / in vitro BBB model

Outline of Final Research Achievements

Epidemiological studies have revealed cognitive dysfunction caused by inorganic arsenic (iAs) exposure, but experimental validation is understood to be difficult. We speculate that cognitive dysfunction following exposure to iAs is caused by tight junction (TJ) injury at the blood-brain barrier (BBB). Validation using the rat in vitro BBB model showed that TJ injury is caused by concentration-dependent exposure to iAs and is also related to the action of Nrf2 and HO-1. This study suggests significant potential for experimental verification of cognitive dysfunction from iAs exposure. An essential result of this research is the identification of methylation as a detoxification mechanism for iAs in the brain. Furthermore, inhibiting TJ injury by antioxidant stress responses has been shown to be a potential preventive measure against cognitive dysfunction.

Free Research Field

衛生学

Academic Significance and Societal Importance of the Research Achievements

無機ヒ素暴露からの認知機能障害に関する解明研究は公衆衛生学において重要な課題である。動物での実験的検証には時間や費用、技術的な問題があった。本研究では、人間や動物の血液脳関門（BBB）を模範したrat in vitro BBB modelの有効性を証明し、当該研究の促進や発展に貢献が期待される。