1998 Fiscal Year Final Research Report Summary
Microdialytic and behavioral pharmacological evaluation of mice offspring prenatally exposed to low-level methylmercury.
| Project/Area Number |
08457124
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Public health/Health science
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
SATOH Hiroshi Tohoku U.Gr.Sch.Med., Professor, 医学部, 教授 (40125571)
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| 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
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| Project Period (FY) |
1996 – 1998
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| Keywords | methylmercury / trans-generation effects / behavioral effects / activity / learning / motor performance / selenium / mice |
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| 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
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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
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