Yoshida Minoru, Honda Akiko, Watanabe Chiho, Satoh Masahiko, Yasutake Akira
Faculty of Human Health Sciences, Hachinohe Gakuin University.
J Toxicol Sci. 2014 Aug;39(4):561-70. doi: 10.2131/jts.39.561.
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.
本研究考察了出生后发育阶段暴露于不同水平零价汞(Hg(0))的小鼠大脑中神经行为变化与基因表达谱改变之间的关系。新生小鼠在出生后第20天前,每天24小时反复暴露于浓度为0.057毫克/立方米(低水平,接近当前阈限值(TLV))和0.197毫克/立方米(高水平)的汞蒸气(Hg(0))中。在12周龄时,基于旷场试验(OPF)中的运动活动变化、被动回避反应试验(PA)中的学习能力以及莫里斯水迷宫(MM)中的空间学习能力来评估行为反应。暴露于低水平Hg(0)的小鼠与对照小鼠在这三项行为测量中未观察到显著差异。另一方面,在OPF任务中,暴露于高水平Hg(0)的小鼠的总运动活动显著降低,中央运动减少。暴露于低水平和高水平Hg(0)的小鼠大脑中的汞浓度分别约为0.4微克/克和1.9微克/克。基因组分析显示,低水平暴露组中有2个基因表达上调,18个基因表达下调,而高水平暴露组中有3个基因表达上调,70个基因表达下调。两组均观察到7个基因表达有类似改变,其中6个基因表达下调,1个基因表达上调。结果表明,大脑中改变基因数量的增加可能与神经行为效应的出现有关,这可能与大脑中的汞浓度有关。此外,暴露于两种浓度Hg(0)后,无论有无神经行为效应,一些共同改变的基因可能是评估发育早期行为效应的敏感生物标志物基因的候选者。