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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一，该子项目和研究者 (PI) 可能已从其他 NIH 来源获得主要资助，因此可以在其他 CRISP 机构中得到体现。列出的是该中心，不一定是帕金森研究者的机构。疾病（PD）是一种使人衰弱的基底神经节神经退行性疾病，其病因难以捉摸。最近，有人提出，除草剂莠去津是美国使用最广泛的农药，与地下水有关。目前，没有数据表明阿特拉津对基底神经节功能的影响，该研究项目探讨了短期接触阿特拉津会导致持续神经毒性的假设。神经毒性的程度取决于受试者的年龄。此外，长期、低水平接触莠去津本身不会产生神经毒性，但会增强典型基底神经节神经毒物（如 1-）的毒性。甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 为了验证这一假设，1、3 和 10 个月大的 C57BL/6 小鼠将进行实验。短期（14 天）或长期（长达 26 周）暴露于不同剂量的莠去津，并在终止莠去津暴露后另外评估多巴胺能神经变性的程度，以获得对莠去津的机制了解。 -诱导的基底神经节神经毒性，将进行纹状体切片和混合中脑培养物的体外实验。