National Institute For Minamata Disease
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Masatake Fujimura Ph.D.
Chief in Pathology Section
Specialty: Neurotoxicology, Neuropharmacology
Laboratory assistants: Ayumi Onitsuka, Kazumi Ichiura, Michiko Fuchigami
The main target organ of methylmercury is cranial nerve system, and the irreversible impairment of neural function is still one of the most important issues. In our section, we are aiming to clarify the causal factor and the characteristic in the neural dysfunction with the methylmercury by the comprehensive approach from molecular levels (gene and protein), cell levels (cultured cell), individual levels (laboratory animal) and human body levels (pathology tissue), and to apply the research results to the diagnosis, prevention and treatment.
Moreover, we have performed hair mercury investigation about the mercury pollution concern areas around the world. Our lab has been specified a reference lab for the determination of mercury in hair for COPHES (Consortium to Perform Human Biomonitoring on a European Scale) from 2011.
Hobby: Sports watching (especially, baseball).



A part of our research achievement was adopted as a cover figure of a toxicology journal (Toxicol. Appl. Pharmacol. Volume 250, Issue 1, January 1, 2011).
Subjects of study and affair
Project research
  • Research on selective cytotoxicity and factors determining individual sensitivity of methylmercury (representative)
Basic research
  • Research on effect of methylmercury to neurite outgrowth and relief of toxicity (representative)
  • Study on the molecular genetic and biochemical factors causing differences of stress responses to methylmercury (collaborator)
  • Marine ecosystem and mercury behavior in Yatsushiro Sea. -Quantitative survey of marine benthic community in Yatsushiro Sea and mercury concentration of several fishes through food web- (collaborator)
  • Feasibility study of methylmercury exposure and adverse cardiovascular effects in experimental animals (collaborator)
  • Research on effect of dietary fibers on excretion of mercury after methylmercury exposure (collaborator)
Affair research
  • Hair mercury examination of areas concerning for mercury pollution around the world (representative)
  • Digitization of histopathological slides of Minamata disease patients for permanent preservation (collaborator)
Committee
  • Chemicals control committee (head)
Study groups
  • Study group on mechanism
  • Working group on risk recognition and information service
  • Research group on regional and global environment
Research achievements
[Original articles]
 Ÿ@Total number of cited items: 207
 Ÿ@IF2011: Impact Factor 2011
  • Bourdineaud JP, Marumoto M, Yasutake A, Fujimura M: Dietary mercury exposure resulted in behavioral differences in mice contaminated with fish-associated methylmercury compared to methylmercury chloride added to diet. J. Biomed. Biotechnol. (IF2011: 2.436), 2012, 681016 (2012).
  • Bourdineaud JP, Laclau M, Maury-Brachet R, Gonzalez P, Baudrimont M, Mesmer-Dudons N, Fujimura M, Marighetto A, Godefroy D, Rostène W, Brèthes D: 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. Int. J. Mol. Sci. (IF2011: 2.598), 13, 7710-7738 (2012).
  • Fujimura M, Cheng J, Zhao W: Perinatal exposure to low dose of methylmercury induces dysfunction of motor coordination with decreases of synaptophysin expression in the cerebellar granule cells of rats. Brain Res. (IF2011: 2.728), 1464, 1-7 (2012).
  • Fujimura M, Usuki F: Differing effects of toxicants (methylmercury, inorganic mercury, lead, amyloid β and rotenone) on cultured rat cerebrocortical neurons: differential expression of Rho proteins associated with neurotoxicity. Toxicol. Sci. (IF2011: 4.652), 126, 506-514 (2012).
  • Cambier S, Gonzalez P, Mesmer-Dudons N, Brèthes D, Fujimura M, Bourdineaud JP: Effects of dietary methylmercury on the zebrafish brain: histological, mitochondrial, and gene transcription analyses. Biometals (IF2011: 2.823), 25, 165-180 (2012).
  • Fujimura M, Matsuyama A, Harvard JP, Bourdineaud JP, Nakamura K: Mercury contamination in humans in upper Maroni, French Guiana between 2004 and 2009. Bull. Environ. Contam. Toxicol. (IF2011: 1.018), 88, 135-139 (2012).
  • Godefroy D, Gosselin RD, Yasutake A, Fujimura M, Combadiere C, Maury-Brachet R, Laclau M, Rakwal R, Melik-Parsadaniantz S, Bourdineaud JP, Rostene W: The chemokine CCL2 protects against methylmercury neurotoxicity. Toxicol. Sci. (IF2011: 4.652), 125, 209-218 (2012).
  • Nakamura M, Yasutake A, Fujimura M, Hachiya N, Marumoto M: Evaluation of brain injury in methylmercury intoxication in terms of choroid plexus function. Arch. Toxicol. (IF2011: 4.674), 85, 911-918 (2011).
  • Usuki F, Yamashita A, Fujimura M: Methylmercury-induced relative selenium deficiency causes oxidative stress through its posttranscriptional effect. J. Biol. Chem. (IF2011: 4.773), 286, 6641-6649 (2011). Faculty of 1000 (Pharmacology and Drug Discovery, Rating 8, Must Read).
  • Bourdineaud JP, Fujimura M, Laclau M, Sawada M, Yasutake A: Deleterious effects in mice of fish-associated methylmercury contained in a diet mimicking the Western populations' average fish consumption. Environ. Int. (IF2011: 5.297), 37, 303-313 (2011).
  • Fujimura M, Usuki F, Kawamura M, Izumo S: Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure. Toxicol. Appl. Pharmacol. (IF2011: 4.447), 250, 1-9 (2011).
  • Fujimura M, Usuki F, Sawada M, Takashima A: Methylmercury induces neuropathological changes with tau hyperphosphorylation mainly through the activation of the c-jun N-terminal kinase pathway in the cerebral cortex, but not in the hippocampus of the mouse brain. Neurotoxicology (IF2011: 3.096), 30, 1000-1007 (2009).
  • Fujimura M, Usuki F, Sawada M, Rostene W, Godefroy D, Takashima A: Methylmercury exposure downregulates the expression of Racl, leads to neuritic degeneration and ultimately apoptosis in cerebrocortical neurons. Neurotoxicology (IF2011: 3.096), 30, 16-22 (2009).
  • Bourdineaud JP, Bellance N, Benard G, Brethes D, Fujimura M, Gonzales P, Marighetto A, Maury-Brachet R, Mormede C, Pedron V, Philippin JN, Rossignol R, Rostene W, Sawada M, Laclau M: Feeding mice with diets containing mercury-contaminated fish flesh from French Guiana: a model for the mercurial intoxication of the Wayana Amerindians. Environ. Health (IF2011: 2.650), 7, 53 (2008).
  • Adachi T, Nagano M, Ebihara T, Imai T, Fujimura M, Suketa Y: Influence of dietary protein levels on the fate of inorganic mercury in mice. J. Health Sci. (present Biol. Pharm. Bull.) (IF2011: 1.657), 54, 207-211 (2008).
  • Cochran SM, Fujimura M, Morris BJ, Pratt JA: Acute and delayed effects of phencyclidine upon mRNA levels of markers of glutamatergic and GABAergic neurotransmitter function in the rat brain. Synapse (IF2011: 2.945), 46, 206-214 (2002).
  • Kohara T, Koyama T, Fujimura M, Tanaka H, Maeda J, Fujimoto T, Yamamoto I, Arita M: Y-931, a novel atypical antipsychotic drug, is less sensitive to oxidative phenomena. Chem. Pharm. Bull. (IF2011: 1.592), 50, 818-821 (2002).
  • Morimoto T, Hashimoto K, Yasumatsu H, Tanaka H, Fujimura M, Kuriyama M, Kimura K, Takehara S, Yamagami K: Neuropharmacological profile of a novel potential atypical antipsychotic drug Y-931 (8-fluoro-12-(4-methylpiperazin-1-yl) -6H-[1] benzothieno[2,3-b][1,5] benzodiazepine maleate). Neuropharmacology (IF2011: 4.814), 26, 456-467 (2002).
  • Kuriyama M, Hashimoto K, Yasumatsu H, Morimoto T, Tanaka H, Fujimura M, Kimura K, Takehara S, Yamagami K: Neuropharmacological examination of a new antipsychotic candidate, Y-931. Jap. J. Psychopharm., 21, 246 (2001). Japanese.
  • Fujimura M, Hashimoto K, Yamagami K: The effect of the antipsychotic drug mosapramine on the expression of Fos protein in the rat brain comparison with haloperidol, clozapine and risperidone. Life Sci. (IF2011: 2.527), 67, 2865-2872 (2000).
  • Fujimura M, Hashimoto K, Yamagami K: Effect of antipsychotic drugs on neurotoxicity, expression of fos-like protein and c-fos mRNA in the retrosplenial cortex after administration of dizocilpine. Eur. J. Pharmacol. (IF2011: 2.516), 398, 1-10 (2000).
  • Hashimoto K, Fujimura M, Yamagami: Dizocilpine-induced neuropathological changes in rat retrosplenial cortex are reversed by subsequent clozapine treatment. Life Sci. (IF2011: 2.527), 66, 1071-1078 (2000).
  • Itoh K, Tomozane H, Hakira H, Sonda S, Asano K, Fujimura M, Sato N, Haga K, Kawakita T: Synthesis and pharmacological properties of novel benzamide derivatives acting as ligands to the 5-hydroxytryptamine 4 (5-HT4) receptor. Eur. J. Med. Chem. (IF2011: 3.346), 34, 1101-1108 (1999).
  • Fujimura M, Mikashima H: Effect of Y-20811, a thromboxane synthetase inhibitor, on photochemically induced cerebral embolism in rabbits. Thromb. Res. (IF2011: 2.440), 70, 233-244 (1993).
[Books]
  • Usuki F, Fujimura M: Effect of methylmercury on cellular signal transduction systems. In: Aschner M and Ceccatelli S (ed.) Methylmercury and neurotoxicity, Current Topics in Neurotoxicity, Springer Science + Business Media, Berlin, 2, 229-240 (2012).
[Patents]
  • Kohara T, Fukunaga K, Fujimura M, Hanano T, Okabe H: Dihydropyrazolopyridine compounds and pharmaceutical use thereof. United States Patent 6977262.
  • Seio K, Tanaka H, Kohara T, Hashimoto K, Fujimura M, Horiuchi H, Yasumatsu H, Kimura K: Condensed thiophene compounds and pharmaceutical use thereof. United States Patent 6455521.
  • Seio K, Tanaka H, Kohara T, Hashimoto K, Fujimura M, Horiuchi H, Yasumatsu H, Kimura K: Fused thiophene compounds and medicinal use thereof. United States Patent 6271225.
  • Kohara T, Fukunaga K, Fujimura M, Hanano T, Okabe H: Dihydropyrazolopyridine compounds and medicinal use thereof. WO2005-501800.
  • Fukunaga K, Okabe H, Kohara T, Fujimura M, Tanaka H, Takanashi S. Aromatic amid compounds. WO2001-081345.
  • Seio K, Tanaka H, Kohara T, Hashimoto K, Fujimura M, Horiuchi H, Yasumatsu H, Kimura K: Condensed thiophene compounds and medicinal use thereof. WO1999-011647, WO2001-072684.
[Invited lectures]
  • Fujimura M: Axonal degeneration by methylmercury contributes neuronal cell death, and inhibition of Rho/ROCK pathway prevents the neurotoxicity. Methylmercury meeting, (2012).
  • Fujimura M: Methylmercury toxicity and Tau protein. Hokuriku University Frontier, Satellite meeting, (2010).
  • Fujimura M: Molecular mechanism of methylmercury-induced neurotoxicity in cerebrocortical neuron. Forum 2008: Pharmaceutical Health and Environmental Toxicology, (2008).
  • Fujimura M: Tau phosphorylation induced by methylmercury. Hokuriku University Frontier, Satellite meeting, (2007).
  • Fujimura M: La maladie de Minamata. Lundis de Saint-Antoine Séminaires, (2006).
[Presentations at International conference]
  • Fujimura M, Usuki F: Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure. 51st Society of Toxicology, (2012).
  • Fujimura M: Neuritic degeneration contributes to methylmercury induced neuronal cell death. NIMD forum 2011, (2011).
  • Fujimura M, Usuki F, Takashima A: Methylmercury induces neuropathological changes with tau hyperphosphorylation mainly through the activation of the c-jun N-terminal kinase pathway in the cerebral cortex, but not in the hippocampus of the mouse brain. 17th International Congress of Neuropathology, (2010).
  • Fujimura M, Usuki F, Rostene W, Godefroy D, Takashima A: Methylmercuryof Rac1 and lead to neuritic degeneration and ultimately apoptosis in cerebrocortical neurons. 49th Society of Toxicology, (2010).
  • Fujimura M: Hair mercury examination of mercury-polluted area in the world. NIMD forum 2009, (2009).
  • Fujimura M, Sawada M, Takashima A: Methylmercury induces Alzheimerfs disease-like Tau phosphorylation in mouse brain. 47th Society of Toxicology, (2008).
  • Fujimura M, Sawada M, Takashima A: Long-term exposure to low-concentration methylmercury induces neuronal cell death via neurite retraction in rat cultured neuron. 8th International conference on mercury as a global pollutant, (2006).
  • Fujimura M, Sawada M, Takashima A: Methylmercury induces Tau degradation and neuronal cell death via Tau hyperphosphorylation in rat cultured neuron. 8th International conference on mercury as a global pollutant, (2006).
  • Fujimura M, Hashimoto K, Yamagami K: The effect of the antipsychotic drug mosapramine on the expression of Fos protein in the rat brain comparison with haloperidol, clozapine and risperidone. 24th Collegium Internationale Neuro Psychopharmacologicum, (2001).
  • Fujimura M, Hashimoto K, Yamagami K: Suppressive effects of clozapine and olanzapine on the expression of Fos protein in rat brain by MK-801. 21st Collegium Internationale Neuro Psychopharmacologicum, (1998).
Research by the external fund
  • Ministry of education, science, sports and culture, grant-in aid for scientific research (S), No. 24221004, 2012-2016, Japan (cooperative)
    [Molecular mechanism on sex immature imprinting and childcare collapse induced by environmental pollutant]
  • Ministry of education, science, sports and culture, grant-in aid for defiant germ research, No. 24659426, 2012-2013, Japan (assignment)
    [Examination on vascular endothelial growth factor as a new molecular target for methylmercury poisoning]
  • Ministry of education, science, sports and culture, grant-in aid for scientific research (C), No. 23590167, 2011-2013, Japan (representative)
    [Experimental research on selective neuronal damage by methylmercury using microdissection method]
  • Ministry of education, science, sports and culture, grant-in aid for scientific research (C), No. 20590135, 2008-2010, Japan (representative)
    [Experimental research on effect of Rho kinase inhibitors against neurological impairment by environmental toxins]
  • Grants from French National Research Agency, ANR n‹ SEST 2005-034, France (assignment)
    ["Santéenvironnement et santé-travail" program]
The main history, academic background, degree, and citation etc.
  • Origin: Sasebo City in Nagasaki Prefecture
  • Bachelor of Science (Kagoshima University)
   ¨ Master of Science (Kagoshima University)
   ¨ Senior researcher (Yoshitomi pharmaceutical industries, present Mitsubishi Tanabe pharma corporation)
   ¨ Doctor of Pharmacology (Kyushu University)
   ¨ Senior researcher (YRING in United Kingdom, present PsyRING)
   ¨ Chief in Physiology Section (National Institute for Minamata Disease)
   ¨ Chief in Pathology Section (National Institute for Minamata Disease)
  • Visiting professor (Bordeaux University in France), 2008-2009
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