Neurobehavioral changes in response to alterations in gene expression profiles in the brains of mice exposed to low and high levels of mercury vapor during postnatal development.
Neurobehavioral changes in response to alterations in gene expression profiles in the brains of mice exposed to low and high levels of mercury vapor during postnatal development.
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DOI：
10.2131/jts.39.561
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发表时间：
2014-08
期刊：
影响因子：
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通讯作者：
Minoru Yoshida;Akiko Honda;C. Watanabe;M. Satoh;A. Yasutake
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文献类型：
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作者：
Minoru Yoshida;Akiko Honda;C. Watanabe;M. Satoh;A. Yasutake
这项研究考察了在出生后发育过程中暴露于不同水平汞(0)的小鼠的神经行为变化与大脑基因表达谱变化的关系。新生小鼠连续暴露于汞蒸气(Hg0)浓度为0.057 mg/m(3)(低水平)和0.197 mg/m(3)(高水平)，持续24小时，直至产后第20天。根据12周龄大鼠旷场运动能力(OPF)、被动回避反应(PA)学习能力和Morris水迷宫(MM)空间学习能力的变化评价动物的行为反应。暴露于低水平汞(0)的小鼠与对照组小鼠之间的三项行为测量结果无显著差异。另一方面，暴露在高水平汞(0)下的小鼠的总运动活动显著减少，在OPF任务中，中枢运动减少。暴露于低水平和高水平汞(0)的小鼠大脑中的汞浓度分别约为0.4μg/g和1.9μg/g。基因组分析显示，低水平暴露组有2个基因表达上调，18个基因表达下调；高水平暴露组有3个基因表达上调，70个基因表达下调。在两组中都观察到了7个基因的表达变化，其中6个基因下调，1个基因上调。结果表明，大脑中改变的基因数量的增加可能参与了神经行为效应的出现，这可能与大脑中汞的浓度有关。此外，在暴露于两种浓度的汞(0)后，一些常见的改变基因可能是在发育早期评估行为影响的敏感生物标记基因。
This study examined the relationship between neurobehavioral changes and alterations in gene expression profiles in the brains of mice exposed to different levels of Hg(0) during postnatal development. Neonatal mice were repeatedly exposed to mercury vapor (Hg(0)) at a concentration of 0.057 mg/m(3) (low level), which was close to the current threshold value (TLV), and 0.197 mg/m(3) (high level) for 24 hr until the 20(th) day postpartum. Behavioral responses were evaluated based on changes in locomotor activity in the open field test (OPF), learning ability in the passive avoidance response test (PA), and spatial learning ability in the Morris water maze (MM) at 12 weeks of age. No significant differences were observed in the three behavioral measurements between mice exposed to the low level of Hg(0) and control mice. On the other hand, total locomotive activity in mice exposed to the high level of Hg(0) was significantly decreased and central locomotion was reduced in the OPF task. Mercury concentrations were approximately 0.4 μg/g and 1.9 μg/g in the brains of mice exposed to the low and high levels of Hg(0), respectively. Genomic analysis revealed that the expression of 2 genes was up-regulated and 18 genes was down-regulated in the low-level exposure group, while the expression of 3 genes was up-regulated and 70 genes was down-regulated in the high-level exposure group. Similar alterations in the expression of seven genes, six down-regulated genes and one up-regulated gene, were observed in both groups. The results indicate that an increase in the number of altered genes in the brain may be involved in the emergence of neurobehavioral effects, which may be associated with the concentration of mercury in the brain. Moreover, some of the commonly altered genes following exposure to both concentrations of Hg(0) with and without neurobehavioral effects may be candidates as sensitive biomarker genes for assessing behavioral effects in the early stages of development.