IN VIVO AND IN VITRO EFFECTS OF THE PESTICIDE ATRAZINE ON BASAL GANGLIA FUNCTION

农药阿特拉津对基底节功能的体内外影响

• 批准号: 7381806
• 负责人: NIKOLAY M FILIPOV
• 金额: $ 8.83万
• 依托单位: MISSISSIPPI STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381806
• 关键词: VIVO; VITRO; EFFECTS; PESTICIDE; ATRAZINE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Parkinson¿s Disease (PD) is a debilitating neurodegenerative disease of the basal ganglia and has an elusive etiology. Recently, a possible link between PD and pesticide exposure has been suggested. The herbicide atrazine is the most widely used pesticide in the US, with ground water contamination being a major concern. Currently, there are no data addressing atrazine effects on basal ganglia function. This research project explores the hypothesis that short-term exposure to atrazine would result in persistent neurotoxicity with the degree of neurotoxicity being dependent on the age of the subjects. Moreover, it is hypothesized that chronic, low-level exposure to atrazine will not be neurotoxic on its own, but it will potentiate the toxicity of a typical basal ganglia neurotoxicant such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To address this hypothesis, C57BL/6 mice, 1, 3, and 10 months of age, will be exposed to various dosages of atrazine for either short-term (14 days) or long-term (up to 26 weeks) and the degree of dopaminergic neurodegeneration will be assessed after termination of atrazine exposure. Additionally, to gain a mechanistic insight on atrazine-induced basal ganglia neurotoxicity, in vitro experiments with striatal slices and mixed mesencephalic cultures will be performed.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。帕金森S病是一种基底节衰弱的神经退行性疾病，其病因难以捉摸。最近，人们提出了帕金森病与农药暴露之间可能的联系。除草剂阿特拉津是美国使用最广泛的杀虫剂，地下水污染是一个主要问题。目前，还没有关于阿特拉津对基底节功能影响的数据。这项研究项目探索了一种假设，即短期暴露于阿特拉津会导致持续的神经毒性，神经毒性的程度取决于受试者的年龄。此外，假设长期、低水平暴露于阿特拉津本身不会产生神经毒性，但它会增强典型的基底节神经毒物，如1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)的毒性。为了解决这一假设，1、3和10个月龄的C57BL/6小鼠将短期(14天)或长期(长达26周)暴露于不同剂量的阿特拉津，并在停止暴露后评估多巴胺能神经变性的程度。此外，为了从机制上深入了解阿特拉津引起的基底节神经毒性，将进行纹状体切片和混合中脑培养物的体外实验。