Role of fetal metallothionein against mercury toxicity after exposure to mercury vapor
Role of fetal metallothionein against mercury toxicity after exposure to mercury vapor
批准号:
14570307
负责人:
YOSHIDA Minoru
金额:
$2.56万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2002
资助国家:
日本
项目状态:
已结题
起止时间:
2002 至 2003
中文摘要
(1)低浓度汞蒸气暴露对金属硫蛋白缺失小鼠的行为影响我们研究了低浓度汞蒸气长期暴露对小鼠神经行为的影响以及脑内金属硫蛋白(MT)亚型在汞所致行为神经毒性中的作用。将不表达MT-Ⅰ和-Ⅱ基因的MT-敲除小鼠和野生型小鼠暴露于0.031-0.119 mg/m^3的Hg 2 O蒸气中,每天6小时,持续23周。暴露后12周和23周,通过旷场测试和被动回避任务评估行为影响。在12周时,两种品系在旷场试验中的总运动活动达到了过度活跃的水平,但被动回避行为不受影响。在第23周进行的行为测试中,与对照组相比,在暴露的MT缺失小鼠中观察到运动活动的显著增加和被动回避反应测试中的学习障碍。然而,Concent ...更多信息 MT敲除小鼠脑内汞含量明显低于野生型小鼠,组织化学评价MT敲除小鼠神经组织也正常。长期暴露于Hg 2 O蒸气后,野生型小鼠的脑MT水平高于MT缺失小鼠。这些结果表明,MT-Ⅰ和MT-Ⅱ在汞蒸气暴露后产生的行为变化中起重要作用。(2)金属硫蛋白基因敲除小鼠产前暴露于汞蒸气后神经行为的变化我们研究了金属硫蛋白基因敲除小鼠产前暴露于元素汞蒸气(Hg 20)后神经行为的变化。将两种品系孕鼠分别以0.50和0.56 mg/m^3的剂量暴露于Hg_2O蒸气中,每天6 h,直至孕18天。在12周龄时,通过旷场自主活动、被动回避反应中的学习能力和Morris水迷宫中的空间学习能力来评价行为学效应。与对照组相比,Hg 2 o暴露的MT基因敲除小鼠雄性的总运动活动显著减少,雌性的被动回避反应学习障碍和Morris水迷宫习得延迟。相反,暴露于Hg 2 o的野生型小鼠在三个行为测量上与对照组没有差异。结果表明,MT基因敲除小鼠比野生型小鼠更容易受到产前汞暴露的行为神经毒性的影响。特别是,与同品系雄性小鼠相比,MT-null雌性小鼠的海马涉及学习性能可能受到显着影响。从这些结果可以认为,胎儿脑中的MT-Ⅰ和MT-Ⅱ具有防止产前暴露于Hg_2O引起的行为效应的作用。少
英文摘要
(1) Behavioral effects of low levels of exposure to mercury vapor in metallothionein-null miceWe 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 … More 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 vaporWe 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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