Research on inciting factor of neurological symptoms following low dose methylmercury exposure in fetal period

• Project/Area Number: 26460187
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental and hygienic pharmacy
• Research Institution: National Institute for Minamata Disease
• Principal Investigator: Fujimura Masatake 国立水俣病総合研究センター, 基礎研究部, 室長 (20416564)
• Co-Investigator(Kenkyū-buntansha): 臼杵 扶佐子 国立水俣病総合研究センター, その他部局等, 部長 (50185013)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 低濃度メチル水銀 / 胎児期曝露 / 神経症状 / メチル水銀 / 小脳 / 神経突起 / シナプス蛋白

Outline of Final Research Achievements

We clarified that a low level methylmercury exposure (5 ppm in drinking water) during fetal period induced neurological symptoms without inducing neuronal cell death through the suppression of eEF1A1 and subsequent nerve hypoplasia in rat cerebellum. Furthermore, we also clarified that a low level methylmercury (10 nM) inhibited the proliferation of neuronal cells through the induction of GSK-3b in neural progenitor cells of rats.

Research Products

• [Journal Article] Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity adn eEF1A1 expression in the rat cerebellum. (2016)
  • Author(s): Fujimura M, Usuki F, Cheng J, Zhao W
  • Journal Title: Toxicology and Applied Pharmacology Volume: 298 Pages: 1-8
  • DOI: 10.1016/j.taap.2016.03.002
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Assessing pre/post-weaning neurobehavioral development for perinatal exposure to low doses of methylmercury. (2015)
  • Author(s): Cheng J, Fujimura M, Bo D.
  • Journal Title: Journal of Environmental Sciences (China) Volume: 38 Pages: 36-41
  • DOI: 10.1016/j.jes.2015.05.027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Low concentrations of methylmercury inhibit neural progenitor cell proliferation associated with up-regulation of glycogen synthase kinase 3β and subsequent degradation of cyclin E in rats. (2015)
  • Author(s): Fujimura M, Usuki F.
  • Journal Title: Toxicology and Applied Pharmacology Volume: 288 Issue: 1 Pages: 19-25
  • DOI: 10.1016/j.taap.2015.07.006
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] メチル水銀毒性とRho蛋白質. (2015)
  • Author(s): 藤村成剛
  • Journal Title: 臨床環境医学 Volume: 24 Pages: 79-83
  • Peer Reviewed
• [Journal Article] Methylmercury causes neuronal cell death through the suppression of the TrkA pathway: In vitro and in vivo effects of TrkA pathway activators. (2015)
  • Author(s): Fujimura M, Usuki F
  • Journal Title: Toxicology and Applied Pharmacology Volume: 282 Issue: 3 Pages: 259-266
  • DOI: 10.1016/j.taap.2014.12.008
  • Peer Reviewed
• [Journal Article] 水銀汚染と生物への影響. 特集: 水銀～その規制動向と処理技術 (2015)
  • Author(s): 藤村成剛
  • Journal Title: 環境浄化技術 Volume: 14 Pages: 1-3
• [Presentation] 低用量メチル水銀のラット胎児期曝露はTrkA-eEF1A1経路の抑制を介して神経突起形成不全およびシナプス恒常性変化を引き起こす. (2015)
  • Author(s): 藤村成剛, 臼杵扶佐子.
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] メチル水銀の胎児期曝露による小脳神経シナプス形成におよぼす影響. (2015)
  • Author(s): 藤村成剛, Cheng J, Zhao W.
  • Organizer: 第42回日本毒性学会学術年会
  • Place of Presentation: 金沢
  • Year and Date: 2015-06-29
  • Invited
• [Presentation] Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure. (2015)
  • Author(s): Fujimura M, Usuki F.
  • Organizer: ASIATOX 2015
  • Place of Presentation: 韓国・済州
  • Year and Date: 2015-06-23
  • Int'l Joint Research / Invited
• [Presentation] メチル水銀毒性とRho蛋白質. (2015)
  • Author(s): 藤村成剛
  • Organizer: 第24回日本臨床環境医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-06
  • Invited
• [Presentation] Low level of methylmercury inhibits cell proliferation through the activation of glycogen synthase kinase 3and subsequent degradation of cyclin E in cortical progenitor cells of rats. (2015)
  • Author(s): Fujimura M, Usuki F
  • Organizer: 54th Society of Toxicology
  • Place of Presentation: 米国・サンディエゴ
  • Year and Date: 2015-03-22 – 2015-03-26
• [Presentation] Activation of TrkA pathway by GM1 ganglioside and its analog prevents methylmercury-induced nerve damage in vitro and in vivo. (2014)
  • Author(s): Fujimura M, Usuki F
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Remarks] 国立水俣病総合研究センター・職員紹介・藤村成剛
  • URL: http://www.nimd.go.jp/kakubu/kiso/fujimura.html
• [Remarks] 職員紹介
  • URL: http://www.nimd.go.jp/kakubu/kiso/fujimura.html