| Project/Area Number |
18K19708
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 58:Society medicine, nursing, and related fields
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
TAKATA Ayako 聖マリアンナ医科大学, 医学部, 教授 (30321897)
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| Co-Investigator(Kenkyū-buntansha) |
人見 敏明 聖マリアンナ医科大学, 医学部, 准教授 (90405275)
曹 洋 聖マリアンナ医科大学, 医学部, 助教 (70793751)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | 無機ヒ素 / モノメチル化ヒ素 / 血液脳関門 / 脳機能障害 / in vitro BBBモデル / iPS細胞 / ヒ素中毒 / メチル化ヒ素化合物 / 化学構造 / 化学価数 / ヒ素 |
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| Outline of Final Research Achievements |
In an in vitro method using rat primary culture cells, the blood-brain barrier (BBB) was set at the mature and the immature stages, and arsenic trioxide (iAs(III)) and the intermediate metabolite monomethylated arsenic (MMA(III)) were added to the cells respectively. The effects on the BBB were evaluated at 6 hours and 24 hours after exposure.
iAs(III) and MMA(III) each induced Nrf2 and HO-1 in dose-dependent manner as oxidative stress effects. These effects were more pronounced at 6 hours than at 24 hours. The effect on the barrier function was evaluated by Western blot (WB) method and immunostaining using Claudin-5 as a marker. The injury appeared in both mature and immature stages of BBB, suggesting that MMA(III) had a stronger effect than iAs(III).
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| Academic Significance and Societal Importance of the Research Achievements |
本研究から、ラット初代培養細胞を用いた試験方法において、BBB機能を成熟及び未成熟期に設定して無機ヒ素とその代謝物の暴露後におけるバリア機能への影響を評価可能とし、ヒトiPS細胞を用いたin vitro試験法への展開に必要な基礎情報を得た。本研究の成果は、グリア細胞へのサイトカインストームによる炎症反応からの神経細胞への障害を検証する技術として有益な可能性があり、現代社会における脳機能障害や認知機能障害に関する研究に貢献する社会的意義がある。
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