Neurological effects of toxic metal exposure in model rodents collected in zones of industrial agriculture on the U.S.-Mexico border

美国-墨西哥边境工业化农业区收集的模型啮齿动物暴露有毒金属对神经系统的影响

• 批准号: 10558449
• 负责人: JONATHAN M CREDO
• 金额: $ 5.27万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10558449
• 关键词: Adult; Agriculture; Animals; Area; Arizona; Basal Ganglia; Behavioral; Biochemical Reaction; Brain; Child; Collaborations; Communities; Consumption; Copper; County; Data; Data Set; Elements; Environmental Pollution; Exposure to; Family; Fellowship; Funding; Gene Expression; Genes; Genetic; Goals; Hair; Health; Housing; Human; Human Volunteers; Incidence; Individual; Industrialization; Kilogram; Link; Lipids; Liquid Chromatography; Manganese; Mass Spectrum Analysis; Mercury; Metabolism; Metal exposure; Metals; Mexico; Micronutrients; Migrant; Modality; Modeling; Motor; Muscle Contraction; Neurologic Effect; Neurotoxins; Organism; Outcome; Output; Pathway Analysis; Pathway interactions; Peer Review; Peromyscus; Persons; Pesticides; Poison; Population; Quantitative Reverse Transcriptase PCR; Reporting; Research; Reservations; Review Literature; Risk; Risk Assessment; Rodent; Rodent Model; Sampling; Seasons; Sentinel; Severity of illness; Site; Source; Spectrometry; Symptoms; Techniques; Tissues; Toxin; Training; Tribes; Underserved Population; United States; Work; bioinformatics pipeline; carcinogenicity; differential expression; dopaminergic neuron; farm worker; ground water; health assessment; improved; insight; ion mobility; landfill; lead exposure; lipid metabolism; lipidomics; metabolic profile; metabolomics; motor disorder; multidisciplinary; nano-string; neurotoxic; neurotoxicity; novel; olfactory bulb; organic base; oxidative damage; pesticide exposure; response; toxic metal; transcriptomics; tribal lands; tribal member; virtual; wasting

ABSTRACT Yuma County is a large agricultural hub of the United States and provides over 90% of the winter leafy greens consumed in the U.S. To maintain high agricultural output, more than 2.6 million kilograms of agrichemicals are used in Yuma County each year. These agrichemicals represent a significant exposure source of toxic chemicals for residents, especially the migrant and seasonal farmworkers and those living near agricultural lands. Previous research focused on organic based pesticides and lead exposure sources, but inorganic metals-based pesticides have not been examined in this area. I performed quantitative metal(loid) analysis of human (n = 323) and rodent (Peromyscus eremicus, n = 300) hair samples and found concentrations of neurotoxic metals (especially Cu and Mn) at levels known to be associated with adverse health outcomes. Following these findings, preliminary transcriptomic analyses demonstrated disrupted genetic pathways, including those associated with lipid metabolism and muscle contraction, in the brains of rodents that I captured from agricultural sites, compared to non-agricultural sites, from Yuma County. Cu and Mn are naturally occurring elements and are essential micronutrients in enzymatic reactions, but both are toxic at high concentrations. Cu causes non-specific oxidative damage in tissues, while Mn accumulates in the basal ganglia and dopaminergic neurons and is linked with behavioral issues in children and motor dysfunction in adults. Farmworkers and communities near agricultural areas with high agrichemical application are an understudied population regarding excessive Cu and Mn exposure. This proposal expands upon my preliminary work that identified elevated concentrations of Cu and Mn in human and rodent hair collected in Yuma County by using the P. eremicus rodent model to investigate transcriptomic and lipidomic responses to exposure. Additionally, I am developing a similar approach in collaboration with the Cocopah Tribe in Yuma County to assess the risk of contaminant exposure in their people. Under the guidance of a multidisciplinary team, I aim to: Aim 1) assess effects of mixed metals exposure on brain gene expression in rodents collected from agricultural vs. non-agricultural regions of Yuma County, using both non-targeted Nanostring and targeted qRT-PCR approaches; Aim 2) assess effects of mixed metals exposure on brain metabolic profiles in rodents from these two exposure regions, using liquid chromatography-ion mobility spectrometry-mass spectrometry; and Aim 3) gather P. eremicus samples on Cocopah Tribal Lands to conduct preliminary exposure risk assessment. This project will provide information on the neurological effects of exposure to metals used in agriculture and aid in developing models that assess health impacts in the underserved population of farmworkers and tribal members in Yuma County.

摘要 尤马县是美国的一个大型农业中心，90%以上的冬季绿叶蔬菜都是由该县提供的 在美国，为了保持高农业产量，超过260万公斤的农用化学品 每年在尤马县使用。这些农用化学品是有毒物质的重要暴露来源。 居民用化学品，特别是外来务工人员和季节性农场工人以及那些居住在农业附近的人 土地。以前的研究主要集中在有机农药和铅接触源上，但无机的 这一领域尚未对金属类农药进行检查。我执行了定量金属(Loid)分析 人(n=323)和啮齿动物(Permyscus eremicus，n=300)毛发样本，发现 神经毒性金属(尤其是铜和锰)在已知与不良健康后果有关的水平上。 根据这些发现，初步的转录分析表明遗传途径被破坏， 包括与脂肪代谢和肌肉收缩有关的那些，在啮齿类动物的大脑中 与来自尤马县的非农业地点相比，从农业地点捕获的。铜和锰是 自然产生的元素，是酶反应中必不可少的微量营养素，但两者在高剂量下都是有毒的 浓度。铜在组织中引起非特异性氧化损伤，而锰在基底物中积累。 神经节和多巴胺能神经元，与儿童的行为问题和运动功能障碍有关 成年人。农化应用较高的农区附近的农场工人和社区是一种 关于过量铜和锰暴露的研究不足的人群。这项建议在我的基础上扩展了 初步工作发现，在2008年收集的人和啮齿动物毛发中铜和锰浓度升高 尤马县利用Eremicus啮齿动物模型研究转录和脂体对 曝光。此外，我正在与尤马的Cocopah部落合作开发一种类似的方法 县评估其人民接触污染物的风险。在多学科的指导下 团队，我的目标是：1)评估混合金属暴露对收集的啮齿动物脑基因表达的影响 来自玉马县农业和非农业地区，使用非靶向纳米线和靶向纳米线 QRT-PCR方法；目的2)评估混合金属暴露对啮齿类动物脑代谢的影响 从这两个暴露区域，采用高效液相色谱-离子迁移率-质谱法； 目的3)采集Cocopah部落土地上的P.eremicus样本，进行初步暴露风险 评估。该项目将提供有关接触金属的神经影响的信息。 农业和援助开发评估服务不足人口健康影响的模型 尤马县的农场工人和部落成员。