Neurotoxicity of Methylmercury in the Visual Cortex

描述(申请人提供)：甲基汞(甲基汞)是一种环境神经毒物，与过去发生的几起大规模慢性和急性中毒事件有关。汞污染仍然是公众健康的一个主要环境问题，特别是对高鱼饮食的人群以及孕妇和哺乳妇女。由于最近有报道称，食用受甲基汞污染的海鲜与神经毒性的潜在风险比我们之前认为的更大，这一担忧已经加剧。急性和慢性甲基汞暴露会扰乱人类和动物的感觉和运动功能，并导致严重的神经毒性。甲基汞中毒在人类和动物中最一致的表现之一是视觉功能障碍。这是以视野的同心收缩为特征的--周边视觉敏感度丧失，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害。这些损害的潜在机制仍然知之甚少，尽管似乎甲基汞诱导的视觉缺陷起源于视觉皮质。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围视野永久性丧失的原因。然而，视觉功能障碍往往发生在视皮层没有或正在发生病变的情况下。因此，视觉缺陷可能是由于甲基汞引起的视皮层某些神经元功能的暂时中断。我们假设甲基汞可能优先影响视觉皮质中特定神经元群体的突触功能。该项目的长期目标是了解甲基汞在视觉系统中引起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质中某些神经元群体的突触功能。其具体目的是确定视觉皮质特定区域或层的神经元及其相关突触功能是否受到甲基汞的选择性影响，以及GABA能反应是否比谷氨酸能反应对甲基汞更敏感。这项研究可能是第一个专门针对甲基汞对中枢视觉功能的慢性影响而设计的研究。这项研究的结果将提供关于甲基汞在视觉系统中选择性神经毒性的具体信息。

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.