Lee Jin-Yong, Yoshida Minoru, Satoh Masahiko, Watanabe Chiho
Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, 464-8650 Japan.
Department of Nursing, Tokyo Junshin University, 2-600 Takiyama-machi, Hachioji, Tokyo, 192-0011 Japan.
Toxicol Res. 2023 Sep 21;40(1):111-124. doi: 10.1007/s43188-023-00210-3. eCollection 2024 Jan.
In this study, we investigated the neurobehavioral alterations and modifications of gene expression in the brains of female mice exposed to low-level mercury vapor and/or methylmercury during postnatal development. The mice were exposed to low-level mercury vapor at a mean concentration of 0.094 mg/m and supplied with tap water containing 5 ppm methylmercury from postnatal day 11 to 12 weeks of age. Behavioral analyses were performed at 17 weeks of age. Total locomotor activity in the open field test and the retention trial performance in the passive avoidance test were significantly reduced in the combined exposure group compared with those in the control group. The differences in locomotor activity and performance in the retention trial at 17 weeks were no longer detected at 45 weeks. These results suggest that the effect of aging on the behavioral abnormalities resulting from postnatal exposure to mercury complexes are not significant. In the microarray analysis of brains in the combined exposure group, the gene expression levels of and were decreased. Real-time RT-PCR analysis confirmed these changes caused by combined mercury exposure, showing significant downregulation of and in the cerebrum. These genes play key roles in the brain as a calcium-activated chloride channel and as a kinase that responds to cellular stress, respectively. Our findings provide insight into the neurobehavioral changes caused by combined mercury exposure.
在本研究中,我们调查了出生后发育期间暴露于低水平汞蒸气和/或甲基汞的雌性小鼠大脑中的神经行为改变和基因表达变化。小鼠从出生后第11天至12周龄期间暴露于平均浓度为0.094毫克/立方米的低水平汞蒸气,并饮用含有5 ppm甲基汞的自来水。在17周龄时进行行为分析。与对照组相比,联合暴露组在旷场试验中的总运动活动和被动回避试验中的记忆保持试验表现显著降低。在45周龄时未再检测到17周龄时运动活动和记忆保持试验表现的差异。这些结果表明,衰老对出生后暴露于汞复合物所致行为异常的影响不显著。在联合暴露组大脑的微阵列分析中,[具体基因1]和[具体基因2]的基因表达水平降低。实时逆转录-聚合酶链反应分析证实了联合汞暴露引起的这些变化,显示大脑中[具体基因1]和[具体基因2]显著下调。这些基因在大脑中分别作为钙激活氯通道和对细胞应激作出反应的激酶发挥关键作用。我们的研究结果为联合汞暴露引起的神经行为变化提供了见解。