Study for target epigenome molecules exposed to low-concentration methylmercury that cause neuronal differentiation effects

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K12341
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 63030:Chemical substance influence on environment-related
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: Kurita Hisaka 岐阜薬科大学, 薬学部, 講師 (00746315)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: メチル水銀 / エピジェネティクス / 神経分化

Outline of Final Research Achievements

Recently, there are concerns about the effect of low-concentration methylmercury (MeHg) on fetal nerve development due to the intake of fish and shellfish by pregnant women. In this study, we investigated the neurological effects of low-concentration MeHg on neural differentiation and its epigenetic mechanism using an in vitro neural differentiation system. We found that epigenome changes mediated by elevation of DNMT1 and HDAC3 and 6 are important for the suppression of neurite outgrowth in MeHg. Furthermore, we found NR4A1 as a target gene related to suppression of neurite extension and decreased neural spike activity by MeHg exposure, and MeHg decreased histone H3 acetylation in the NR4A1 gene promoter region, increased DNA methylation, and decreased CREB binding to the NR4A1 gene promoter.

Free Research Field

毒性学、衛生学、薬物治療学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、未だ世界レベルでは、議論の余地が残っている低濃度MeHg曝露による胎児への影響について、新たな科学的知見を与えるものである。また、本成果で見出されたエピジェネティクスに注目した分子メカニズムの知見は、今後の胎盤を通過する新たな化合物の神経分化への影響の毒性影響や分子メカニズムを予測する上で、役立つと考える。