Experimental research on selective neuronal damage by methylmercury using microdissection method

2013 Fiscal Year Final Research Report

• 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
• Keywords: メチル水銀 / マイクロダイセクション / 小脳顆粒細胞

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] 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] 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
• [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
  • Year and Date: 20130000
• [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
  • Year and Date: 20130000
• [Remarks]
  • URL: http://www.nimd.go.jp/kakubu/kiso/fujimura.html