2023 Fiscal Year Final Research Report
Interaction between inorganic arsenic and manganese in brain neuronal damage due to combined exposure to inorganic arsenic and manganese
| Project/Area Number |
21K10422
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 58020:Hygiene and public health-related: including laboratory approach
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
Toshiaki Hitomi 聖マリアンナ医科大学, 医学部, 准教授 (90405275)
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| Co-Investigator(Kenkyū-buntansha) |
高田 礼子 聖マリアンナ医科大学, 医学部, 教授 (30321897)
山内 博 聖マリアンナ医科大学, 医学部, 教授 (90081661)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | ヒ素 / マンガン / 複合暴露 / 血液脳関門 / 認知能力障害 / 認知機能障害 / 小児 / 成人 |
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| Outline of Final Research Achievements |
Inorganic arsenic (iAs) and manganese (Mn) are causative agents of cognitive dysfunction, but the effects of combined exposure are unknown. We speculate that the cognitive dysfunction caused by iAs exposure may have a mechanism of action whereby tight junction (TJ) injury of the blood-brain barrier (BBB) occurs first, followed by stepwise injury of glial cells and neurons by iAs that have penetrated the BBB. Mn is more likely to transfer to brain tissue than iAs, but the detailed mechanisms of BBB on TJ are unknown. In validation experiments using the rat in vitro BBB model, combined exposure to iAs and Mn increased BBB TJ injury compared to exposure to iAs alone. Furthermore, validation using human brain neurons and rat astrocytes confirmed that combined exposure to iAs and Mn was associated with increased toxicity compared to exposure to each alone. This study highlights the need for research to elucidate the cognitive dysfunction in combined exposure to iAs and Mn.
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| Free Research Field |
衛生学
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| Academic Significance and Societal Importance of the Research Achievements |
無機ヒ素（iAs）やマンガン（Mn）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。さらに、慢性ヒ素中毒の発生地域ではMnの同時暴露も存在し、複合暴露による影響の検証が必要である。rat in vitro-BBB modelは、iAsとMnの複合暴露ではBBBのTJ傷害の増強の確認が可能となり、実験動物の代替法になり得るin vitro-BBB modelであった。
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