Manganese neurotoxicity
Manganese neurotoxicity
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DOI：
10.1196/annals.1306.009
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Aschner, M
中科院分区：
文献类型：
--
作者：
Dobson, AW;Erikson, KM;Aschner, M
锰是一种必需的微量元素，是许多普遍存在的酶反应所必需的。虽然人类很少发生锰缺乏，但已知在某些职业环境中，通过吸入含锰粉尘而发生锰中毒。大脑特别容易受到这种过量锰的影响，在那里积累会导致一种被称为锰中毒的神经退行性疾病。这种疾病的特征被描述为帕金森样症状。这两种疾病之间的相似之处可以部分解释为，与锰中毒的其他脑区相比，基底节积累了大部分多余的锰，基底节功能障碍也是帕金森病的病因。有人提出，已经处于神经退行性疾病高风险的人群也可能更容易受到锰神经毒性的影响，这突显了研究在汽油中使用有争议的化合物甲基环戊二烯基锰三甲酰(MMT)来增加辛烷值对人类健康影响的重要性。锰水平升高可导致神经元功能障碍和死亡的机制尚不清楚。然而，线粒体扰动产生的氧化应激可能是受影响的中枢神经系统细胞死亡的关键事件。我们对原代培养的星形胶质细胞的研究表明，它们是抵御锰诱导的神经毒性的关键成分。此外，氧化应激在锰中毒进展中的作用的证据也在这里进行了综述。
Manganese is an essential trace element and it is required for many ubiquitous enzymatic reactions. While manganese deficiency rarely occurs in humans, manganese toxicity is known to occur in certain occupational settings through inhalation of manganese-containing dust. The brain is particularly susceptible to this excess manganese, and accumulation there can cause a neurodegenerative disorder known as manganism. Characteristics of this disease are described as Parkinson-like symptoms. The similarities between the two disorders can be partially explained by the fact that the basal ganglia accumulate most of the excess manganese compared with other brain regions in manganism, and dysfunction in the basal ganglia is also the etiology of Parkinson's disease. It has been proposed that populations already at heightened risk for neurodegeneration may also be more susceptible to manganese neurotoxicity, which highlights the importance of investigating the human health effects of using the controversial compound, methylcyclopentadienyl manganese tricarbonyl (MMT), in gasoline to increase octane. The mechanisms by which increased manganese levels can cause neuronal dysfunction and death are yet to be elucidated. However, oxidative stress generated through mitochondrial perturbation may be a key event in the demise of the affected central nervous system cells. Our studies with primary astrocyte cultures have revealed that they are a critical component in the battery of defenses against manganese-induced neurotoxicity. Additionally, evidence for the role of oxidative stress in the progression of manganism is reviewed here.