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

甲基汞（MeHg）已被证明是一种神经毒素。由于发育中的大脑对甲基汞特别敏感，产前低水平的甲基汞暴露会导致包括神经行为改变在内的几种不良反应。然而，关于甲基汞的长期暴露仍有许多问题有待阐明。为了研究低剂量长期甲基汞暴露对神经行为的影响，雌性C57BL/6Cr小鼠在8周龄时，在交配前4周口服含有0、1或5 ppm（作为汞）甲基汞的饮食。小鼠在妊娠期和哺乳期连续暴露于甲基汞，所得到的后代也同样暴露于甲基汞。分别在幼鼠12、56、103周龄时进行开放性实验和Morris水迷宫实验。在12周龄的野外试验中，MeHg暴露显著增加了雌性小鼠的排尿次数和排便次数，降低了雌性小鼠的运动活性。在这一年龄，雄性mehg暴露小鼠海马CA3区细胞外谷氨酸动员模式明显增加，提示行为改变可能与大脑生化变化有关。在56周龄时，尽管MeHg暴露在野外试验中没有引起任何显著影响，但在103周龄时，MeHg暴露再次降低了运动活动。在Morris水迷宫测试中，MeHg暴露增加了大鼠在12、56和103周龄到达隐藏平台的时间。结果表明，长期低剂量甲基汞暴露对儿童情绪行为和空间学习能力有严重的不良影响；衰老揭示了甲基汞暴露对老年小鼠空间学习能力的影响，部分掩盖了甲基汞暴露对老年小鼠情绪参数的影响。此外，本文还从神经行为发育的角度探讨了硒、金属硫蛋白-1、金属硫蛋白- 2和生长环境的作用。最后，还研究了产前和成年暴露的综合影响。少

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