Neurotoxicological mechanism of methylmercury induced by low-dose and long-term exposure in mice:: Oxidative stress and down-regulated Na+/K+-ATPase involved
Neurotoxicological mechanism of methylmercury induced by low-dose and long-term exposure in mice:: Oxidative stress and down-regulated Na+/K+-ATPase involved
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DOI：
10.1016/j.toxlet.2007.11.004
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发表时间：
2008-02-15
影响因子：
3.5
通讯作者：
Lin-Shiau, Shoei-Yn
中科院分区：
文献类型：
--
作者：
Huang, Chun-Fa;Hsu, Chuan-Jen;Lin-Shiau, Shoei-Yn
甲基汞（MeHg）是一种强效的神经毒物，很容易穿过血脑屏障（BBB），在大脑区域积聚，造成严重的不可逆转的损害。然而，甲基汞的神经毒性作用和作用机制仍不清楚，特别是在低剂量和长期暴露下。本研究试图探讨低剂量（0.05 mg/kg/d）甲基汞（甲基汞污染区可能的暴露剂量）连续7周给药后对小鼠运动活动和听觉脑干反应（ABR）系统变化的时间过程的毒性作用。结果表明，口服MeHg 1周后，在旋转棒（60转/分）上的滞留时间优先减少。MeHg连续暴露3周后，运动活动参数的移动距离和刻板印象-1发作次数显著增加，垂直平面进入次数逐渐减少。在给药4-6周期间，发现ABR逐渐进行性异常（听力阈值升高，绝对潜伏期和波间潜伏期延长）。这些损伤与脑区和/或其他组织中显著的汞积累和生化改变相关，包括脂质过氧化（LPO）生成的增加、Na+/K+- atp酶活性和一氧化氮（NO）水平的影响。这些发现表明，氧化应激/Na+/K+- atp酶/NO信号在低剂量和长期暴露MeHg诱导的神经毒性作用的潜在机制中起作用。2007爱思唯尔爱尔兰有限公司版权所有。
Methylmercury (MeHg), a potent neurotoxicant, easily passes through the blood-brain barrier (BBB), accumulates in the brain regions and causes severe irreversible damage. However, the neurotoxic effects and action mechanisms of MeHg are still unclear, especially in low-dose and long-term exposure. In this study, we attempted to explore the toxic effects of low-dose MeHg (0.05 mg/kg/day), which was the possible exposed dose by ingestion in MeHg-contaminated areas, on the time course of changes in locomotor activities and auditory brainstem response (ABR) system after administration for 7 consecutive weeks in mice. The results showed that the retention time on the rotating rod (60 rpm) was preferentially decreased after 1-week oral administration with MeHg. The locomotor activities parameters of ambulatory distances and stereotype-1 episodes were significantly increased and vertical-plane entries were progressively decreased after MeHg exposure in 3 consecutive weeks. Gradually progressive abnormality of ABR (increase in hearing thresholds, prolonged absolute and interwave latencies) was found during 4-6 weeks administration of MeHg. These impairments correlated with significant Hg accumulation and biochemical alterations in brain regions and/or other tissues, including the increase of lipid peroxidation (LPO) production, influence of Na+/K+-ATPase activities and nitric oxide (NO) levels were found. These findings provide evidence that the signaling of oxidative stress/Na+/K+-ATPase/NO plays a role in the underlying mechanisms of the neurotoxic effects induced by low-dose and long-term exposure of MeHg. (c) 2007 Elsevier Ireland Ltd. All rights reserved.