GLUTATHIONE AND DOPAMINERGIC NEURONAL SURVIVAL

谷胱甘肽和多巴胺能神经元的存活

• 批准号: 6185105
• 负责人: KEN NAKAMURA
• 金额: $ 4.17万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6185105
• 关键词: cell growth regulation; digital imaging; dopamine; fluorescence microscopy; fluorimetry; free radicals; genetically modified animals; glutamate ammonia ligase; glutathione; glutathione peroxidase; hydrogen peroxide; laboratory mouse; mesencephalon; methylphenyltetrahydropyridine; neuroprotectants; oxidative stress; tissue /cell culture

DESCRIPTION (Adapted from applicant's abstract): An increased production of reactive oxygen species is thought to be critical to the pathogenesis of Parkinson's disease. Furthermore, a growing body of evidence indicates that alterations in the glutathione system, and specifically the detoxification of hydrogen peroxide by glutathione peroxidase (GPx), may play a central role in the development of this oxidative stress. In this study, we will use GPx knockout (GPxKO) mice and recombinant adenoviruses to examine the significance of GPx and glutathione (GSH) to the survival of dopaminergic neurons. In addition, we will investigate how adding the putative exogenous source of free radical 1-methyl-4-phenylpyridine affects the role of GPx in handling oxidative stress in dopaminergic neurons. We will begin by examining the survival of dopaminergic neurons in dissociated mesencephalic cultures which are designed to minimize glial contamination. In addition, we will use digital imaging microfluorimetry to measure levels of free radicals and GSH in individual dopaminergic and nondopaminergic neurons. Subsequently, we will use an in vivo paradigm to study the GSH system in a more physiologic environment.

描述（改编自申请人的摘要）：增加生产 活性氧被认为对于疾病的发病机制至关重要 帕金森病。 此外，越来越多的证据表明 谷胱甘肽系统的改变，特别是解毒 谷胱甘肽过氧化物酶 (GPx) 产生的过氧化氢可能发挥重要作用 在这种氧化应激的发展中发挥作用。 在本研究中，我们将 使用 GPx 敲除 (GPxKO) 小鼠和重组腺病毒来检查 GPx 和谷胱甘肽 (GSH) 对多巴胺能细胞存活的重要性 神经元。 此外，我们将研究如何添加假定的外源性 自由基1-甲基-4-苯基吡啶的来源影响GPx的作用 处理多巴胺能神经元的氧化应激。 我们将从 检查分离中脑中多巴胺能神经元的存活 旨在最大限度地减少神经胶质污染的培养物。 此外， 我们将使用数字成像微荧光测定法来测量游离水平 单个多巴胺能和非多巴胺能神经元中的自由基和谷胱甘肽。 随后，我们将使用体内范例来研究 GSH 系统 更多的生理环境。