| Project/Area Number |
14570307
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | St.Marianna University School of Medicine |
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Principal Investigator |
YOSHIDA Minoru St.Marianna University School of Medicine, Associated Professor, 医学部, 助教授 (80081660)
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| Co-Investigator(Kenkyū-buntansha) |
KAZAMA Akio St.Marianna University School of Medicine, Assistant Professor, 医学部, 講師 (60288149)
WATANABE Chiho The University of Tokyo, Associated Professor, 大学院医学系研究科, 助教授 (70220902)
SATOH Masahiko Gifu Pharmaceutical University, Associated Professor, 薬学部, 助教授 (20256390)
前山 史朗 聖マリアンナ医科大学, 医学部, 助教授 (70121217)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | metallothionein / mercury concentration / mercury vapor / neurobehavioral change / prenatal exposure / open field test / MT null-mice / passive avoidance response / オープンフィールテスト / メタロチオネイン / 受動的回避実験 |
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| Research Abstract |
(1) Behavioral effects of low levels of exposure to mercury vapor in metallothionein-null mice
We studied the neurobehavioral effects of prolonged exposure to low concentrations of mercury (Hg^o) vapor and the role of metallothionein (MT) isoforms present in the brain on the behavioral neurotoxicity caused by mercury. MT-null mice that do not express MT-I and -II genes and wild type mice were exposed to Hg^o vapor at 0.031-0.119 mg/m^3 for 6hr per day for 23 weeks. The behavioral effects were evaluated with an open field test and passive avoidance tasks at 12 and 23 weeks after exposure. At 12 weeks, total locomotor activity in the open field test reached hyperactive levels in both strains, but the passive avoidance behavior was un-affected. In the behavioral test performed at 23 weeks, a significant increase in locomotor activity and a learning disability in the passive avoidance response test were observed in the exposed MT-null mice as compared with the controls. However, the concent
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ration of mercury in the brain was significantly lower in MT-null mice than wild type mice and the nervous tissues of MT-null mice were also normal on histochemical evaluation. Brain MT levels were higher in wild type than MT-null mice following prolonged exposure to Hg^o vapor. These results suggest that MT-I and -II in the brain play an important role in the behavioral changes produced following exposure to Hg^o vapor.
(2) Neurobehavioral changes in metallothionein-null mice prenatally exposed to mercury vapor
We studied the neurobehavioral effects of prenatal exposure of MT-null ad wild-type mice following prenatal exposure to elemental mercury vapor (Hg^o). Both strains of pregnant mice were repeatedly exposed to Hg^o vapor at 0.50 and 0.56 mg/m^3 for 6h per a day until 18th day from gestation. The behavioral effects were evaluated with locomotor activity in the open field, learning ability in the passive avoidance response and spatial learning ability in the Morris water maze at 12 weeks of age. Hg^o-exposed MT-null mice showed a significant decrease in total locomotor activity in males, and a learning disability in the passive avoidance response and a retarded acquisition in the Morris water maze in females as compared with the control. On the contrary, Hg^o-exposed wild-type mice did not differ from controls on three behavioral measurements. The results indicate that MT-null mice would be more susceptible than wild-type mice to the behavioral neurotoxcity of prenatal Hg^o exposure. Especially, hippocampus involving a learning performance of MT-null female mice may be significantly affected by mercury compared with male of same strain. From these results, it is considered that MT-I and -II in fetal brain has a role preventing the behavioral effects caused by prenatal exposure to Hg^o. Less
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