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Neurobehavioral effects of low-dose long-term methylmercury exposures in mice

Research Project

Project/Area Number 13307014
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionTohoku University

Principal Investigator

SATOH Hiroshi  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40125571)

Co-Investigator(Kenkyū-buntansha) KAMEO Satomi  Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (40312558)
NAKAI Kunihiro  Tohoku University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助教授 (00291336)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥53,170,000 (Direct Cost: ¥40,900,000、Indirect Cost: ¥12,270,000)
Fiscal Year 2003: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2002: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2001: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Keywordsmethylmercury / prenatal exposure / low-dose exposure / behavioral sciences / selenium / oxidative stress / mercury / aging
Research Abstract

Methylmercury (MeHg) has been shown to be a neurotoxin. Since developing brain is especially sensitive to MeHg, low levels of prenatal exposure to MeHg causes several adverse effects including neurobehavioral changes. However, many questions remain to be elucidated about the long-term exposure to MeHg. To examine the neurobehavioral effects of low-dose long-term MeHg exposures, female C57BL/6Cr mice at 8 weeks old were orally given MeHg with diet containing 0, 1 or 5 ppm (as Hg) MeHg for 4 weeks before mating. The mice were continuously exposed to MeHg during gestation and lactation, and the offspring obtained were also exposed with the same diet. Neurobehavioral examinations including open field test and Morris water-maze test were performed when the offspring were at 12, 56 or 103 weeks old. In open field test at 12 weeks old, MeHg exposure significantly increased the number of urination and defecation, and decreased the locomotion activity in female mice. At this age, an abnormal pa … More ttern of extracellular glutamate mobilization could be seen at hippocampus CA3 region of male MeHg-exposed mice, suggesting that behavioral changes might be related to the biochemical changes occurred in the brain. At 56 weeks old, although MeHg exposure did not cause any significant effect in open field test, MeHg exposure again decreased the locomotion activity at 103 weeks old. In Morris water-maze test, MeHg exposure increased the time to reach to the hidden platform at 12, 56 and 103 weeks old. These results suggest that low-dose long-term MeHg exposure caused serious adverse effects on emotional behaviors and spatial learning ability ; aging unmasked the effects of MeHg exposure on the spatial learning ability, while it partially masked the effects on the emotional parameters in elderly mice. In addition, the roles of selenium, metallothionein (MT)-1,2, and growth environment were examined from the viewpoints of neurobehavioral development, respectively. Finally, the combined effects of prenatal and adulthood exposures were also examined. Less

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Nakai K, Satoh H: "Developmental neurotoxicity following prenatal exposures to methylmercury and PCBs in humans from epidemiological studies."Tohoku Journal of Experimental Medicine. 196. 89-98 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakai K, Oka T, Suzuki K, Okamura K, Hosokawa T, Sakai T, Nakamura T, Takahasi M, Satoh H.: "Effects of perinatal exposure to environmentally persistent organic pollutants and heavy metals on neurobehavioral development in Japanese children : II. Protocol and description of study cohort."Organohalogen Compounds. 59. 389-390 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arisawa K., Matsumura T., Tohyama C., Saito H.,, Satoh H., Nagai M., Morita M., Suzuki T.: "Fish intake, plasma ω-3 polyunsaturated fatty acids, and polychlorinated dibenzo-p-dioxins/polychlorinated dibenzo-furans and co-planar polychlorinated biphenyls in the blood of the Japanese population."International Archives of Occupational and Environmental Health. 76. 205-215 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki K., Nakai K., Oka T., Hosokawa T., Okamura K., Sakai T., Satoh H.: "Effects of perinatal exposure to environmentally persistent organic pollutants and chemicals on neurobehavioral development in Japanese children : III. maternal smoking confounds neonatal neurobehavioral status."Organohalogen Compounds. 65. 218-221 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoh H.: "Behavioral teratology of mercury and its compounds."Tohoku Journal of Experimental Medicine. 201. 1-9 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwasaki Y., Sakamoto M., Nakai K., Oka T., Dakeishi M., Iwata T., Satoh H., Murata K.: "Estimation of daily mercury intake from seafood in Japanese women : Akita cross-sectional study."Tohoku Journal of Experimental Medicine. 200. 67-73 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakai K., Keita S., Oka T., Murata K., Sakamoto M., Okamura K., Hosokawa T., Takeo S., Nakamura T., Saito Y., Kurokawa N., Kameo S., Satoh H.: "The Tohoku Study of Child Development : A Cohort Study of Effects of Perinatal Exposures to Methylmercury and Environmentally Persistent Organic Pollutants on Neurobehavioral Development in Japanese Children."Tohoku Journal of Experimental Medicine. 202(submitted). 227-238 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakai K, Satoh H: "Evelopmental neurotoxicity following prenatal exposures to methylmercury and PCBs in humans from epidemiological studies."Tohoku Journal of Experimental Medicine. 196. 89-98 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakai K, Oka T, Suzuki K, Okamura K, Hosokawa T, Sakai T, Nakamura T, Takahasi M, Sato: "Effects of perinatal exposure to environmentally persistent organic pollutants and heavy metals on neurobehavioral development in Japanese children : II. Protocol and description of study cohort."Organohalogen Compounds. 59. 389-390 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arisawa K., Matsumura T., Tohyama C., Saito H., Satoh H., Nagai M., Mouita M., Suzuki T.: "Fish intake, plasma ω-3 polyunsaturated fatty acids, and polychlorinated dibenzo-p-dioxins/polychlorinated dibenzo-furans and co-planar polychlorinated biphenyls in the blood of the Japanese population."International Archives of Occupational and Environmental Health. 76. 205-215 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki K., Nakai K., Oka T., Hosokawa T., Okamura K., Sakai T., Satoh H.: "Effects of perinatal exposure to environmentally persistent organic pollutants and chemicals on neurobehavioral development in Japanese children : III. maternal smoking confounds neonatal neurobehavioral status."Organohalogen Compounds. 65. 218-221 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoh H.: "Behavioral teratology of mercury and its compounds."Tohoku Journal of Experimental Medicine. 201. 1-9 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwasaki Y., Sakamoto M., Nakai K., Oka Dakeishi M., Iwata T., Satoh H., Murata K.: "Estimation of daily mercury intake from seafood in Japanese women : Akita cross-sectional study."Tohoku Journal of Experimental Medicine. 200. 67-73 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakai K., Keita S., Oka T., Murata K., Sakamoto M., Okamura K., Hosokawa T., Takeo S., Nakamura T., Saito Y., Kurokawa N., Kameo S., Satoh H.: "The Tohoku Study of Child Development : A Cohort Study of Effects of Perinatal Exposures to Methylmercury and Environmentally Persistent Organic Pollutants on Neurobehavioral Development in Japanese Children."Tohoku Journal of Experimental Medicine. 202. 27-238 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 佐藤 洋: "メチル水銀と健康リスク評価"日本衛生学雑誌. 59. 113 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arisawa K., Matsumura T., Tohyama C., Saito H., Satoh H., Nagai M., Morita M., Suzuki T.: "Fish intake, plasma ω-3 polyunsaturated fatty acids, and polychlorinated dibenzo-p-dioxins/polychlorinated dibenzo-furans and co-planar polychlorinated biphenyls in the blood of the Japanese population"International Archives of Occupational and Environmental Health. 76. 205-215 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakai K., Keita S., Oka T., Murata K., Sakamoto M., Okamura K., Hosokawa T., Takeo S., Nakamura T., Saito Y., Kurokawa N., Kameo S., Satoh H.: "The Tohoku Study of Child Development : A Cohort Study of Effects of Perinatal Exposures to Methylmercury and Environmentally Persistent Organic Pollutants on Neurobehavioral Development in Japanese Children"Tohoku Journal of Experimental Medicine. 202(submitted). 227-238 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuki K., Nakai K., Oka T., Hosokawa T., Okamura K., Sakai T., Satoh H.: "Effects of perinatal exposure to environmentally persistent organic pollutants and chemicals on neurobehavioral development in Japanese children : III. maternal smoking confounds neonatal neurobehavioral status"Organohalogen Compounds. 65. 218-221 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Satoh H.: "Behavioral teratology of mercury and its compounds"Tohoku Journal of Experimental Medicine. 201. 1-9 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iwasaki Y., Sakamoto M., Nakai K., Oka T., Dakeishi M., Iwata T., Satoh H., Murata K.: "Estimation of daily mercury intake from seafood in Japanese women : Akita cross-sectional study"Tohoku Journal of Experimental Medicine. 200. 67-73 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakai K, Satoh H: "Developmental neurotoxicity following prenatal exposures to methylmercury and PCBs in humans from epidemiological studies"Tohoku Journal of Experimental Medicine. 196. 89-98 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hozawa A. et al.: "Relationship between personality and self-measured blood pressure value at home : the Ohasam a study"Clinical and Experimental Hypertension. 24. 115-123 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arisawa K, et al.: "Fish intake, plasma w-3 polyunsaturated fatty acids, and polychlorinated dibenzo-p-dioxins/polychlorinated dibenzo-furans and co-planar polychlorinated biphenyls in the blood of the Japanese population"International Archives of Occupational and Environmental Health. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura T, et al.: "A comparative analysis of certified environmental reference materials using CALUXTM assay and high resolution GC/MS"Organohalogen Compounds. 58. 381-384 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakai K, et al.: "Effects of perinatal exposure to environmentally persistent organic pollutants and heavy metals on neurobehavioral development in Japanese children : II. Protocol and description of study cohort"Organohalogen Compounds. 59. 389-390 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohkubo T, et al.: "Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure : the Ohasam a study"Journal of Hypertension. 57(2). 229-235 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kurokawa N, n et al.: "Association of BMI with the beta3-adrenergic receptor gene polymorphism in Japanese : meta-analysis"Obesity Research. 9(12). 806-809 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsubono Y, et al.: "Green tea and the risk of gastric cancer in Japan"N Eng J Med. 344. 633-636 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Imai Y, et al.: "Usefulness of blood pressure measurements in assessing the effect of treatment in a single-blind placebo-controlled open trial"Journal of Hypertension. 19. 179-185 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kusano-Tsunoh, A, et al.: "Effects of family-togetherness on the food selection by primary and junior high school students : family-togetherness means better food"Tohoku Journal of Experimental Medicine. 194. 121-127 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakai K, et al.: "Effects of perinatal exposure environmentally persisent organic pollutants and heavy metals on neurobehavioral development in Japanese children : an interim report"Organohalogen Compounds. 53. 254-255 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 仲井邦彦, 他: "内分泌撹乱物質の健康影響に関する疫学研究から-周産期曝露の影響を中心として-"最新医学. 57(2). 229-235 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Satoh H, et al.: "NIMC Forum 2001 - Mercury Research : Today and Tommorow -"National Institute for Minamata Disease. 147 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakai K, et al.: "US-Japan worKshop on human health effects of low dose methylmercury exposure"National Institute for Minamata Disease. 213 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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