Neurotoxicity of Maneb and Roundup

代森锰和农达的神经毒性

• 批准号: 7382795
• 负责人: VANESSA A FITSANAKIS
• 金额: $ 15万
• 依托单位: KING UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-10 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382795
• 关键词: Address; Affect; Agricultural Crops; Agriculture; Agrochemicals; Animal Model; Antioxidants; Basal Ganglia; Biological Models; Caenorhabditis elegans; Chemicals; Communities; Complex; Count; Data; Disease; Dose; Environment; Esters; Etiology; Experimental Designs; Exposure to; Fluorescence; Foundations; General Population; Genes; Glean; Globus Pallidus; Glutathione S-Transferase; Glycine max; Goals; Green Fluorescent Proteins; Herbicides; Human; In Vitro; Industrial fungicide; Injury; Investigation; Isoprostanes; Label; Lead; Licensing; Ligase; Link; Lipid Peroxidation; Longevity; Maize; Maneb; Manganese; Marketing; Measures; Membrane Potentials; Microscopy; Minor; Mitochondria; Molecular; Nematoda; Nerve Degeneration; Neurites; Neurodegenerative Disorders; Neurons; Oxidative Stress; Paraquat; Parkinson Disease; Parkinsonian Disorders; Pathway interactions; Patients; Pattern; Pesticides; Phenotype; Play; Population; Predisposition; Prevalence; Principal Investigator; Production; Proteins; Public Health; Reporting; Research Design; Resistance; Response Elements; Rodent Model; Role; Rotenone; Roundup; Seasons; Sequential Treatment; Soybeans; Testing; Time; Toxic Actions; Toxic Environmental Substances; Toxic effect; Transcriptional Activation; Up-Regulation; Visual; Wheat; Work; Zea mays; exposed human population; farmer; glyphosate; hazard; in vivo; in vivo Model; inhibitor/antagonist; manganese ethylenebis(dithiocarbamate); mitochondrial dysfunction; mitochondrial membrane; nervous system disorder; neuron loss; neurotoxic; neurotoxicity; novel; pesticide exposure; programs; response; rural area; tetramethylrhodamine; toe corn; toxicant

DESCRIPTION (provided by applicant): In accordance with the goals set forth by NIEHS, this project seeks to examine the role of pesticides in the etiology of Parksinon's disease (PD). Numerous reports have suggested a link between the on-set of PD and an agricultural environment, which includes pesticide usage. Patients with PD are also known to have mitochondrial dysfunction. Interestingly, many argochemicals are also known mitochondrial inhibitors. The long-term goal of this project is to understand the relationship of two toxicants, the fungicide maneb and the glyphosate-containing herbicide Roundup, to neuronal toxicity. Using the nematode Caenorhabditis elegans (C. elegans) as a model organism, we will test the hypothesis that exposure to multiple agrochemicals, specifically maneb and Roundup, leads to neuronal degeneration. Additionally, we hypothesize that sequential exposure to these pesticides leads to increased oxidative stress. The hypothesis will be tested through two specific aims: (1) to determine whether exposure to maneb or Roundup affects neuronal populations known to be vulnerable in either PD or manganese neurotoxicity; and (2) to determine whether exposure to maneb or Roundup induces the up-regulation of proteins associated with the production of oxidative stress. In order to complete this study, we will use genetically modified C. elegans with various neuronal populations or antioxidant proteins tagged with green fluorescent protein (GFP). Worms will be exposed to varying concentrations of maneb or Roundup, separately, to determine whether they induce neuronal degeneration or oxidative stress as assessed by fluorescent microscopy. Subsequent studies will examine whether sequential treatment of these two pesticides results in increased toxicity. Results from these novel studies will further our understanding of the neurotoxic effects of multiple pesticide exposures. Additioanlly, they will provide evidence about this ability of these chemicals to induce mitochondrial inhibition in vivo. It is anticipated that data gleaned from these studies will further our understanding not only of pesticide neurotoxicity, but also of the mechanism through which environmental toxicants may facilitate the etiology of idiopathic Parkinson's disease. These studies are particularly important to public health because of the increased use of Roundup, and similar herbicides, by the general public and the agricultural community. Although the main ingredient in Roungup is relatively non-toxic, recent data shows that when the chemical is mixed for commercial usage, the final product may be more toxic. Additionally, this work will examine the effects of exposure to multiple pesticides, which is more likely to occur in human exposures.

描述（由申请人提供）：根据NIEHS设定的目标，本项目旨在研究农药在帕金森病（PD）病因学中的作用。许多报告表明，PD的发生与农业环境之间存在联系，其中包括农药的使用。帕金森病患者也有线粒体功能障碍。有趣的是，许多焦化物也是已知的线粒体抑制剂。该项目的长期目标是了解两种毒物，杀菌剂maneb和含有草甘膦的除草剂Roundup与神经元毒性的关系。以秀丽隐杆线虫（C. elegans）为模式生物，我们将检验暴露于多种农用化学品，特别是马耐布和农达，导致神经元退化的假设。此外，我们假设连续暴露于这些农药会导致氧化应激增加。该假设将通过两个特定目的进行检验：(1)确定暴露于锰或农达是否会影响已知易患帕金森病或锰神经毒性的神经元群；(2)确定暴露于马草或农达是否会诱导与氧化应激产生相关的蛋白质上调。为了完成这项研究，我们将使用带有绿色荧光蛋白（GFP）标记的不同神经元群或抗氧化蛋白的转基因秀丽隐杆线虫。蠕虫将分别暴露于不同浓度的马草或农达中，以确定它们是否会诱导神经元变性或氧化应激，通过荧光显微镜进行评估。随后的研究将检查这两种农药的顺序处理是否会导致毒性增加。这些新研究的结果将进一步加深我们对多种农药暴露的神经毒性作用的理解。此外，他们将提供证据证明这些化学物质在体内诱导线粒体抑制的能力。预计从这些研究中收集到的数据不仅将进一步加深我们对农药神经毒性的理解，而且还将进一步了解环境毒物可能促进特发性帕金森病病因的机制。这些研究对公众健康尤其重要，因为普通公众和农业社区越来越多地使用农达和类似的除草剂。虽然农达的主要成分是相对无毒的，但最近的数据显示，当这种化学品混合用于商业用途时，最终产品的毒性可能更大。此外，这项工作将检查接触多种农药的影响，这更有可能发生在人类接触中。