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Microdialytic and behavioral pharmacological evaluation of mice offspring prenatally exposed to low-level methylmercury.

Research Project

Project/Area Number 08457124
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Public health/Health science
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

SATOH Hiroshi  Tohoku U.Gr.Sch.Med., Professor, 医学部, 教授 (40125571)

Co-Investigator(Kenkyū-buntansha) DEJIMA Yasushi  Kyorin U.Sch.Health Sci., Lecturer, 保健学部, 講師 (00237025)
WATANABE Chiho  Tokyo U.Graduate Sch.Med., Assoc.Professor, 医学系研究科, 助教授 (70220902)
仲井 邦彦  東北大学, 医学部, 講師 (00291336)
KOYAMA Hiroshi  Gumma U.Sch.Nursing, Professor
小山 洋  東北大学, 医学部, 助教授 (30143192)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥3,700,000 (Direct Cost: ¥3,700,000)
Keywordsmethylmercury / trans-generation effects / behavioral effects / activity / learning / motor performance / selenium / mice / 胎生期曝露 / 神経伝達物質 / ドパミン / マウス / オープンフィールド試験 / 放射状迷路試験 / ビーム・バランス試験 / ノルエピネフリン
Research Abstract

This study aims at providing basic information for the risk evaluation of human populations with long-term, low-level exposure to methylmercury. Emphasis was on the latent effects of prenatal exposure. Thus, the neurobehavioral effects of prenatal methylmercury exposure were evaluated in mice, focusing on the differential susceptibility among various behavioral functions. Pregnant ICR mice were injected with 0.3-1 mgHg/kg/day of methylmercury from day 10 to 18 of gestation. The behavioral function of the offspring was evaluated by open-field test, radial maze, and balance beam from Weaning to approx. 10 months age. Function of glutamatergic system in the hippocampus was evaluated by microdialysis In addition, modification of the neurotoxicity of methyhnercury by selenium nutrition and heat as confounding factors was also examined.
The results obtained in this study can be summarized as follows :
1) the open-field test, often used as a test for activity level and emotionality, was proved … More to be a sensitive and reproducible technique to evaluate the effect of prenatal methylmercury, and superior to the radial maze or the balance-beam test. It is necessary to identify a human equivalent for this test through further behavioral and/or neurochemical analysis. On the other hand, it is also necessary to refine and improve the technique for evaluation of learning and motor functions.
2) the microdialysis study showed that the hippocampal glutamatergic system responded to the prenatal methylmercury exposure. Considering that the exposure level was low and that the microdialytic evaluation was done at 10 month of age which was remote from the cessation of the exposure, the glutamatergic system may be a sensitive target for prenatal methylmercury.
3) two possible underlying mechanism for the neurotoxicity of prenatal methylmercury, namely oxidative stress and imbalance of the thyroid hormone in fetal brain was also evaluated. Both of them appeared to be responsible to some extent and further studies. Less

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Watanabe C.et al.: "In utero methylmercury exposure differeutially affects the activities of selenoenzymes in the fetal mouse brain" Environmental Research. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Watanabe C.et al.: "In utero exposure to methylmercury and Se deficiency converge on the neruobehavioral outcome in mice" Neurotoxicology and Teratology. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Watanabe C.et al.: "The effect of prenatal methylmercury exposure on the GSH level and lipid peroxidation in the fetal brain" Tohoku Experimental Journal of Medicine. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Watanabe C.et al.: "Deficiency of selenium enhances the K^+-induced release of dopamine in the striatum of mice" Neuroscience Letters. 236. 49-52 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yin K.et al.: "Growth and behavioral changes in mice prenatally exposed to methylmercury and heat." Neurotoxicology and Teratology. 19. 65-71 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Watanabe, C., K.Yoshida, Y.Kasanuma and H.Satoh: "In utero methylmercury exposure differentially affects the activities of selenoenzymes in the fetal mouse brain" Environmental Research. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Watanabe, C., K.Yin, Y.Kasanuma and H.Satoh: "In utero exposure to methylmercury and Se deficiency converge on the neurobehavioral outcome in mice" Neurotoxicology and Teratology. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Watanabe, C., Y.Kasanuma, Y.Dejima and H.Satoh: "The effect of prenatal methylmercury exposure on the GSH level and lipid peroxidation in the fetal brain and placenta of mice" Tohoku Journal of Experimental Medicine. 187. 121-126 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Watanabe, C., Y.Kasanuma and H.Satoh: "Deficiency of selenium enhances the K^+-induced release of dopamine in the striatum of mice" Neuroscience Letters. 236. 49-52 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yin, K., C.Watanabe, H.Inaba and H.Satoh: "Growth and behavioral cahgnes in mice prenatally exposed to methylmercury and heat" Neurotoxicology and Teratology. 19. 65-71 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Watanabe C.et al.: "In utero methylmercury exposure differentially affects the activities of selenoenzymes in the fetal mouse brain" Environmental Research. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Watanabe C.et al.: "In utero exposure to methylmercury and Se deficiency converge on the neruobehavioral outcome in mice" Neurotoxicology and Teratology. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Watanabe C.et al.: "The effect of prenatal methylmercury exposure on the GSH level and lipid peroxidation in the fetal brain" Tohoku Experimental Journal of Medicine. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Watanabe C.et al.: "Deficiency of selenium enhances the K+-induced release of dopamine in the striatum of mice" Neuroscience Letters. 236. 49-52 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yin K.et al.: "Growth and behavioral changes in mice prenatally exposed to methylmercury and heat." Neurotoxicology and Teratology. 19. 65-71 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Watanabe C.et al.: "Deficiency of selenium enharces the K±induced release of dopomine in the stniatum of mid." Neuroscience Letters. 236. 49-52 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 渡辺・吉田・小山・笠沼・佐藤: "マウス胎児期におけるメチル水銀曝露が母体胎児系Se含有酵素の活性に及ぼす影響" Biomed Research an Trace Elewouts. 8. 199-200 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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