Mechanisms of methylmercury-induced neurotoxicity: evidence from experimental studies.
Mechanisms of methylmercury-induced neurotoxicity: evidence from experimental studies.
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DOI：
10.1016/j.lfs.2011.05.019
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发表时间：
2011-10-10
期刊：
影响因子：
6.1
通讯作者：
Aschner, Michael
中科院分区：
文献类型：
--
作者：
Farina, Marcelo;Rocha, Joao B. T.;Aschner, Michael
关键词：
神经系统疾病是常见的，昂贵的，并可能导致持久的残疾。虽然大多数未知，一些环境毒物是公认的神经系统疾病和亚临床脑功能障碍的原因。最著名的神经毒素之一是甲基汞（MeHg），这是一种普遍存在的环境毒物，可导致动物和人类长期的神经和发育缺陷。在水生环境中，甲基汞会在鱼类体内积累，这是人类接触甲基汞的主要来源。尽管几次甲基汞中毒事件有助于了解这种神经毒剂在人类中引起的临床症状和组织学变化，但实验研究在阐明介导甲基汞诱导的神经毒性的分子机制方面至关重要。本文综述了甲基汞神经毒性分子机制的实验研究结果。虽然全貌尚未被揭露，在体外培养的细胞，分离的线粒体和组织切片的基础上，以及在体内的研究主要是基于使用啮齿动物，点在细胞内钙稳态的损害，改变谷氨酸稳态和氧化应激的重要事件在甲基汞诱导的神经毒性。这些事件之间的潜在关系进行了讨论，特别强调由甲基汞诱导的兴奋性毒性和氧化应激引发的神经毒性循环。发育中的大脑对甲基汞毒性的特殊敏感性，硒蛋白的关键作用和硒化合物的潜在保护作用也进行了讨论。这些概念提供了了解甲基汞神经毒性的生物化学基础，有助于发现抵消这种毒性的内源性和外源性分子，并提供消除这种恶性循环的有效手段。
Neurological disorders are common, costly, and can cause enduring disability. Although mostly unknown, a few environmental toxicants are recognized causes of neurological disorders and subclinical brain dysfunction. One of the best known neurotoxins is methylmercury (MeHg), a ubiquitous environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. In the aquatic environment, MeHg is accumulated in fish, which represent a major source of human exposure. Although several episodes of MeHg poisoning have contributed to the understanding of the clinical symptoms and histological changes elicited by this neurotoxicant in humans, experimental studies have been pivotal in elucidating the molecular mechanisms that mediate MeHg-induced neurotoxicity. The objective of this mini-review is to summarize data from experimental studies on molecular mechanisms of MeHg-induced neurotoxicity. While the full picture has yet to be unmasked, in vitro approaches based on cultured cells, isolated mitochondria and tissue slices, as well as in vivo studies based mainly on the use of rodents, point to impairment in intracellular calcium homeostasis, alteration of glutamate homeostasis and oxidative stress as important events in MeHg-induced neurotoxicity. The potential relationship among these events is discussed, with particular emphasis on the neurotoxic cycle triggered by MeHg-induced excitotoxicity and oxidative stress. The particular sensitivity of the developing brain to MeHg toxicity, the critical role of selenoproteins and the potential protective role of selenocompounds are also discussed. These concepts provide the biochemical bases to the understanding of MeHg neurotoxicity, contributing to the discovery of endogenous and exogenous molecules that counteract such toxicity and provide efficacious means for ablating this vicious cycle.
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影响因子：
10.4
作者：
Clarkson TW
通讯作者：
Clarkson TW
DOI：
10.1002/neu.480230915
发表时间：
1992-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
CHOI, DW
通讯作者：
CHOI, DW
影响因子：
4.7
作者：
BROOKES, N;KRISTT, DA
通讯作者：
KRISTT, DA
影响因子：
4.5
作者：
Carvalho, Marcia C.;Franco, Jeferson L.;Farina, Marcelo
通讯作者：
Farina, Marcelo
影响因子：
3.8
作者：
Carvalho, Marcia C.;Nazari, Evelise M.;Muller, Yara M. R.
通讯作者：
Muller, Yara M. R.