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的目标，该项目旨在检查农药在Parksinon病病因（PD）中的作用。许多报告表明，PD的现场与农药使用在内的农业环境之间有联系。 PD患者也已知线粒体功能障碍。有趣的是，许多Argochemicals也是已知的线粒体抑制剂。该项目的长期目标是了解两种有毒物质，杀菌剂Maneb和含草甘膦的除草剂综述与神经元毒性的关系。我们将使用线虫秀丽隐杆线虫（秀丽隐杆线虫）作为模型生物，我们将检验以下假设：暴露于多种农业化学物质，特别是MANEB和综述会导致神经元变性。此外，我们假设对这些农药的顺序暴露会导致氧化应激增加。该假设将通过两个具体目的进行检验：（1）确定接触MANEB还是综述是否会影响已知在PD或锰神经毒性中易受伤害的神经元种群； （2）确定暴露于MANEB或综述是否诱导与氧化应激产生有关的蛋白质的上调。为了完成这项研究，我们将使用具有各种神经元种群或用绿色荧光蛋白（GFP）标记的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MANEB或综述中，以确定它们是通过荧光显微镜评估的神经元变性还是氧化应激。随后的研究将检查对这两种农药的顺序治疗是否导致毒性增加。这些新研究的结果将进一步了解多种农药暴露的神经毒性作用。 additioanly，他们将提供有关这些化学物质在体内诱导线粒体抑制作用的能力的证据。预计从这些研究中收集的数据不仅将进一步了解农药神经毒性，而且还将对环境有毒物质可能促进特发性帕金森氏病的病因的机制。这些研究对公共卫生尤为重要，因为公众和农业社区的综述和类似除草剂的使用越来越大。尽管Roungup中的主要成分相对无毒，但最近的数据表明，当化学物质混合以用于商业用法时，最终产物可能会更具毒性。此外，这项工作将研究暴露于多种农药的影响，这种杀虫剂在人类暴露中更有可能发生。