2021 Fiscal Year Final Research Report
Investigation of molecular mechanism of neurological symptoms induced by diphenylarsinic acid and search for curative agents
Project/Area Number |
19K12345
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 63030:Chemical substance influence on environment-related
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Research Institution | Meijo University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 有機ヒ素化合物 / アストロサイト / 神経症状 / 小脳 / ジフェニルアルシン酸 |
Outline of Final Research Achievements |
Diphenylarsinic acid (DPAA) was one of non-natural arsenic compounds found in the well water in Kamisu, Ibaraki, Japan in 2003, which induced neurological symptoms in people having used this well water. Here, we tried to elucidate the underling mechanism of neurological symptoms by DPAA, and to propose a mechanism-based treatment for DPAA intoxication. DPAA caused aberrant astrocyte activation including MAP kinase activation in rat cultured cerebellar astrocytes. Here, we revealed that 1) important cellular signaling pathways such as calpain and NF-κB involved in aberrant astrocyte activation; 2) DPAA induced the same aberrant activation in normal human cerebellar astrocytes as in rat astrocytes; 3) thiol-containing compounds (N-acetylcysteine, etc.) might be more promising chemicals than so-called antioxidants for suppressing DPAA-induced abnormal activation; 4) agents suppressing DPAA-induced aberrant astrocyte activation could not necessarily show a recovery-promoting effect.
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Free Research Field |
神経毒性学
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Academic Significance and Societal Importance of the Research Achievements |
ヒ素化合物汚染は今後も重要な課題であり、今回のDPAAについても神栖の事例が示すように正確な由来等は未だわかっておらず日本国内で再び発生する可能性は十分にあり、さらに中国を含むアジア諸国や欧米でも事故が発生する可能性がある。このような事故がまた発生する前に、事故発生時に迅速に対応するための情報を提供できるよう努める。また無機ヒ素との神経影響の表現型の相違の理由を考察しながら、世界を汚染するヒ素化合物の複雑極まる生体影響の理解と対策に貢献したい。
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