Neurotoxicity of Methylmercury in the Visual Cortex

描述（由申请人提供）：甲基汞（MeHg）是一种环境神经毒物，是过去发生的几起大规模慢性和急性中毒事件的原因。汞污染仍然是公共卫生的一个主要环境问题，特别是对以大量鱼类饮食的人口以及孕妇和哺乳期妇女而言。由于最近有报告称，食用受甲基汞污染的海鲜与神经毒性的潜在风险比我们以前认为的更大有关，因此这种担忧更加严重。急性和慢性接触甲基汞会破坏人类和动物的感觉和运动功能，并导致严重的神经毒性。人类和动物中甲基汞中毒最常见的表现之一是视觉功能障碍。其特征在于视野的同心收缩-周边视觉灵敏度丧失，而中央视觉几乎不受影响。与视觉缺陷相对应的是视皮层中的区域选择性病理损伤。这些损害的潜在机制仍然知之甚少，虽然它似乎是甲基汞诱导的视觉缺陷起源于视觉皮层。甲基汞诱导的视皮层区域选择性病理改变被认为是导致周边视野永久丧失的原因。然而，视觉功能障碍往往发生在没有或正在进行的病理变化的视觉皮层。因此，视觉缺陷可能是由于甲基汞诱导的视觉皮层中某些神经元功能的暂时中断。我们推测，甲基汞可能会优先影响突触功能的一个特定群体的神经元在视觉皮层。本项目的长期目标是了解甲基汞诱导的视觉系统区域选择性神经毒性的细胞和分子基础。作为第一步，本项目专门设计来确定甲基汞是否优先影响视觉皮层中某些神经元群体的突触功能。具体目的是确定神经元及其相关的突触功能在一个特定的区域或层的视觉皮层的影响，选择性地由甲基汞和GABA能反应是否更敏感的甲基汞比是amatergic反应。这项研究可能是第一个专门设计来检查甲基汞对中枢视觉功能的慢性影响。这项研究的结果将提供具体信息的选择性神经毒性的甲基汞在视觉系统。

DESCRIPTION (provided by applicant): Methylmercury (MeHg) is an environmental neurotoxicant that is responsible for several massive chronic and acute poisoning events occurred in the past. Mercury pollution remains a major environmental concern for public health, particularly for populations with high-fish diet and pregnant and nursing women. This concern has been heightened due to recent reports that dietary consumption of MeHg contaminated seafood is associated with greater potential risk of neurotoxicity than we previously thought. Acute and chronic MeHg exposure disrupts sensory and motor functions and causes severe neurotoxicity in humans and animals. One of the most consistent manifestations of MeHg poisoning in humans and animals is the visual functional disturbance. This is characterized by a concentric constriction of the visual fields - the peripheral visual sensitivity is lost whereas the central vision is virtually unaffected. Corresponding to the visual deficits are region-selective pathological lesions in the visual cortex. The underlying mechanisms for these impairments remain poorly understood, although it appears that the MeHg-induced visual deficits originate in the visual cortex. MeHg-induced region-selective pathological alterations in the visual cortex are thought to be responsible for the permanent loss of the peripheral visual fields. However, visual functional disturbances often occurred in the absence of or proceeding pathological changes in the visual cortex. Thus, the visual deficits could be due to MeHg-induced temporary disruption of certain neuronal function in the visual cortex. We hypothesize that MeHg may preferentially affect synaptic function of a specific population of neurons in the visual cortex. The long-term objective of this project is to understand the cellular and molecular bases for MeHg-induced region-selective neurotoxicity in the visual system. As an initial step, the present project is designed specifically to determine if MeHg preferentially affects synaptic function of certain populations of neurons in the visual cortex. The specific aims are to determine if neurons and their associated synaptic function in a particular region or layer of the visual cortex are affected selectively by MeHg and if GABAergic responses are more sentitive to MeHg than are glutamatergic responses. This study could be the first one designed specifically to examine the chronic effects of MeHg on the central visual function. Results of this study will provide specific information about the selective neurotoxicity of MeHg in the visual system.