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资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。帕金森氏病（PD）是一种基底神经节的衰弱性神经退行性疾病，其病因不明。最近，PD和农药暴露之间可能存在联系。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，尚无阿特拉津对基底神经节功能影响的数据。本研究项目探讨的假设是，短期接触阿特拉津将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，据推测，长期低水平接触阿特拉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-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个月大的C57 BL/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，并将在阿特拉津暴露终止后评估多巴胺能神经变性的程度。此外，为了获得对阿特拉津诱导的基底神经节神经毒性的机理认识，将进行纹状体切片和混合中脑培养物的体外实验。