| Project/Area Number |
18H03379
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 63030:Chemical substance influence on environment-related
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| Research Institution | Gunma University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
竹下 章 (財)冲中記念成人病研究所, その他部局等, 研究員 (20322646)
配島 旭 (はい島 旭) 早稲田大学, 人間科学学術院, 講師(任期付) (70555672)
武田 茂樹 群馬大学, 大学院理工学府, 教授 (80282854)
下川 哲昭 高崎健康福祉大学, 健康福祉学部, 教授 (90235680)
宮崎 航 弘前大学, 保健学研究科, 教授 (90512278)
細井 延武 群馬大学, 大学院医学系研究科, 准教授 (90543570)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2020: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | 内分泌かく乱 / 甲状腺ホルモン / 脳発達 / 内分泌かく乱化学物質 / エピゲノム / エストロゲン / 核内受容体 / 遺伝子発現 / エピジェネティック |
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| Outline of Final Research Achievements |
The aim of this study was to investigate the effect of environmental chemicals on the thyroid hormone (TH)-mediated signal transduction using various levels of experiment starting from in silico docking analysis to behavioral analysis. The hydroxylated PCB, which was originally to be used, became unavailable due to restriction in Japan. Instead, isoflavones, PFOS, gadolinium contrast agents, etc. were used. In isoflavones, genistein, daidzein and its metabolite equol exerted their action by crosstalk with several receptors such as TH and estrogen receptors and promoted neurite development and astrocyte migration to affect brain development. For PFOS, its exposure caused various abnormal behaviors and suppressed long-term depression of Purkinje cells, which are target cells for TH. Furthermore, the gadolinium contrast agents also acted by crosstalk of multiple receptors. In particular, the signal transduction of integrin αvβ3, which is a membrane receptor for TH, was disturbed.
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| Academic Significance and Societal Importance of the Research Achievements |
低用量で毒性を発揮する環境化学物質の多くはホルモン受容体に作用し，ホルモン作用を修飾することがわかっている。特に，発達期中枢神経系への曝露により非可逆的な脳発達障害が生じることがわかっているが，作用機構は明らかではない。そこで本研究では分子レベルから行動レベルまで多段階の試験系を用いて，体系的に作用機構を明らかにすることを目指した。本研究により環境化学物質の毒性発現メカニズムが明らかになり，それを社会に向けて発信することで，環境化学物質に対する注意意識の向上が図れるとともに，新たな予防対策の発案にもつながることが期待される。
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