Effects of methylmercury on spinal cord afferents and efferents-A review.
Effects of methylmercury on spinal cord afferents and efferents-A review.
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DOI：
10.1016/j.neuro.2016.12.007
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发表时间：
2017-05
期刊：
影响因子：
3.4
通讯作者：
Atchison WD
中科院分区：
文献类型：
--
作者：
Colón-Rodríguez A;Hannon HE;Atchison WD
甲基汞（MeHg）是一种环境神经毒物，对公众健康有重要影响。它很容易在暴露的人体中积累，主要是在神经元组织中。急性或慢性接触甲基汞会导致中枢神经系统和脊髓神经元严重的神经元功能障碍;易感神经元群体的功能障碍会导致神经退化，至少部分是通过钙离子介导的途径。尽管甲基汞很容易穿过血脑屏障，但周围神经元的生化和形态变化先于中枢脑区的变化。因此，这表明，脊髓传入和传出的独特特点，可以提高其敏感性甲基汞毒性。瞬时受体电位（TRP）离子通道是一类在脊髓传入神经中高度表达的Ca 2+可渗透的阳离子通道，以及其他感觉和内脏器官。这些通道可以以多种方式激活，包括直接通过化学刺激物或间接通过细胞内储存细胞器释放Ca 2+。早期的研究表明，甲基汞与异源TRP相互作用，尽管甲基汞对感觉神经元的毒性机制可能涉及与差异表达的TRP群体之间更复杂的相互作用。在脊髓传出神经中，N-甲基-D-天冬氨酸（NMDA）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和可能的红藻氨酸（KA）类谷氨酸受体被认为在甲基汞诱导的神经毒性中起主要作用。具体而言，钙渗透AMPA受体，这是丰富的运动神经元，已被确定为参与甲基汞诱导的神经毒性。在这篇综述中，我们将描述可能有助于甲基汞诱导的脊髓传入和传出神经元变性的机制，包括可能的介质，如独特表达的钙离子通道。
Methylmercury (MeHg) is an environmental neurotoxicant of public health concern. It readily accumulates in exposed humans, primarily in neuronal tissue. Exposure to MeHg, either acutely or chronically, causes severe neuronal dysfunction in the central nervous system and spinal neurons; dysfunction of susceptible neuronal populations results in neurodegeneration, at least in part through Ca2+-mediated pathways. Biochemical and morphologic changes in peripheral neurons precede those in central brain regions, despite the fact that MeHg readily crosses the blood-brain barrier. Consequently, it is suggested that unique characteristics of spinal cord afferents and efferents could heighten their susceptibility to MeHg toxicity. Transient receptor potential (TRP) ion channels are a class of Ca2+-permeable cation channels that are highly expressed in spinal afferents, among other sensory and visceral organs. These channels can be activated in numerous ways, including directly via chemical irritants or indirectly via Ca2+ release from intracellular storage organelles. Early studies demonstrated that MeHg interacts with heterologous TRPs, though definitive mechanisms of MeHg toxicity on sensory neurons may involve more complex interaction with, and among, differentially-expressed TRP populations. In spinal efferents, glutamate receptors of the N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and possibly kainic acid (KA) classes are thought to play a major role in MeHg-induced neurotoxicity. Specifically, the Ca2+-permeable AMPA receptors, which are abundant in motor neurons, have been identified as being involved in MeHg-induced neurotoxicity. In this review, we will describe the mechanisms that could contribute to MeHg-induced spinal cord afferent and efferent neuronal degeneration, including the possible mediators, such as uniquely expressed Ca2+-permeable ion channels.