Experimental research on selective neuronal damage by methylmercury using microdissection method

• Project/Area Number: 23590167
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental 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): USUKI Fusako 国立水俣病総合研究センター, 臨床部, 部長 (50185013)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: メチル水銀 / マイクロダイセクション / 小脳顆粒細胞 / 国際情報交換 / フランス / 選択的神経細胞障害 / 中毒学 / 環境系薬学 / 薬学

Research Abstract

We isolated granule, Purkinje and molecular layer's neurons in rat cerebellum by using microdissection system and performed real-time PCR analyses for anti-oxidative enzymes. The results suggest that low expression of anti-oxidative enzymes (Mn-SOD, GPx1 and TRxR1) causes CGCs vulnerability to MeHg toxicity.
Next, neurobehavioral analyses revealed that exposure to a low level of MeHg during developmental caused a significant deficit in the motor coordination of rats. The expression of synaptophysin, a marker protein for synaptic formation, significantly decreased in cerebellar granule cells. These results showed that exposure to low-dose MeHg during development induces the dysfunction of motor coordination due to changes of synaptic homeostasis in cerebellar granule cells.

Research Products

• [Journal Article] Low in situ expression of antioxidative enzymes in rat cerebellar granular cells susceptible to methylmercury (2014)
  • Author(s): Fujimura M, Usuki F
  • Journal Title: Arch. Toxicol Volume: 89 Pages: 109-113
• [Journal Article] Low in situ expression of antioxidative enzymes in rat cerebellar granular cells susceptible to methylmercury (2014)
  • Author(s): Fujimura M, Usuki F
  • Journal Title: Arch. Toxicol. Volume: 88 Issue: 1 Pages: 109-113
  • DOI: 10.1007/s00204-013-1089-2
  • Peer Reviewed
• [Journal Article] Neurobehavioral effects, c-Fos/Jun expression and tissue distribution in rat offspring prenatally co-exposed to MeHg and PFOA : PFOA impairs Hg retention (2013)
  • Author(s): Cheng J, Fujimura M, Zhao W, Wang W
  • Journal Title: Chemosphere Volume: 91 Pages: 758-764
• [Journal Article] Neurobehavioral effects, c-Fos/Jun expression and tissue distribution in rat offspring prenatally co-exposed to MeHg and PFOA: PFOA impairs Hg retention (2013)
  • Author(s): Cheng J, Fujimura M, Zhao W, Wang W
  • Journal Title: Chemosphere Volume: 91 Pages: 758-764
  • Peer Reviewed
• [Journal Article] Effects of methylmercury contained in a diet mimicking the Wayana Amerindians contamination through fish consumption : mercury accumulation, metallothionein induction, gene expression variations, and role of the chemokine CCL2 (2012)
  • Author(s): Bourdineaud JP, Laclau M, Maury-Brachet R, Gonzalez P, Baudrimont M, Mesmer-Dudons N, Fujimura M, Marighetto A, Godefroy D, Rostène W, Brèthes D
  • Journal Title: Int. J. Mol. Sci Volume: 13 Pages: 7710-7738
• [Journal Article] Perinatal exposure to low dose of methylmercury induces dysfunction of motor coordination with decreases of synaptophysin expression in the cerebellar granule cells of rats (2012)
  • Author(s): Fujimura M, Cheng J, Zhao W
  • Journal Title: Brain Res Volume: 1464 Pages: 1-7
  • NAID: 130005483670
• [Presentation] Low in situ expression of antioxidative enzymes in rat cerebellar granular cells susceptible to methylmercury (2013)
  • Author(s): Fujimura M, Usuki F
  • Organizer: 第36回日本分子生物学会年会
• [Presentation] Perinatal exposure to low dose of methylmercury induces dysfunction of motor coordination with decreases of synaptophysin expression in the cerebellar granule cells of rats (2013)
  • Author(s): Fujimura M, Cheng J, Zhao W
  • Organizer: 52^<nd> Society of Toxicology
• [Presentation] メチル水銀による翻訳伸長因子eEF1Aの発現低下 (2013)
  • Author(s): 藤村成剛
  • Organizer: 平成25年度メチル水銀研究ミーティング
  • Place of Presentation: 東京
  • Invited
• [Presentation] メチル水銀の選択的細胞傷害 -マイクロダイセクション法を用いた各種神経細胞における抗酸化酵素の発現解析- (2012)
  • Author(s): 藤村成剛
  • Organizer: 平成24年度メチル水銀・カドミウム研究ミーティング
  • Place of Presentation: 東京
  • Invited
• [Remarks]
  • URL: http://www.nimd.go.jp/kakubu/kiso/fujimura.html
• [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] 国立水俣病総合研究センター
  • URL: http://www.nimd.go.jp/