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.

抽象的 尤马县是美国的大型农业枢纽，提供了超过90％的冬季绿叶 在美国消费以维持高农业产量，超过260万公斤的杂货店是 每年在尤马县使用。这些agrichemicals代表了有毒的重要暴露来源 居民，尤其是移民和季节性农民的化学品，以及居住在农业附近的人 土地。先前的研究重点是有机农药和铅暴露来源，但无机 在该地区尚未检查基于金属的农药。我进行了定量金属（LIE）分析 人（n = 323）和啮齿动物（peromyscus ermeticus，n = 300）头发样品并发现的浓度 神经毒性金属（尤其是CU和MN），已知与不良健康结果有关的水平。 遵循这些发现，初步转录组分析表明，遗传途径中断了， 包括与脂质代谢和肌肉收缩相关的那些，在啮齿动物的大脑中 与尤马县的非农业场所相比，从农业场所捕获。 Cu和Mn是 天然存在的元素，是酶促反应中必不可少的微量营养素，但两者在高中都是有毒的 浓度。 CU在组织中引起非特异性氧化损伤，而MN积聚在基础上 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。具有高度应用的农业地区附近的农场工人和社区是 对过度CU和MN暴露的人口进行了研究。该提议扩大了我的 在人类和啮齿动物头发中识别出升高的Cu和Mn浓度的初步工作 Yuma县通过使用Eremeticus啮齿动物模型来研究转录组和脂肪组的反应 接触。此外，我正在与尤马的可可帕部落合作开发类似的方法 县评估其人民污染物的风险。在多学科的指导下 团队，我的目标是：目标1）评估混合金属暴露对收集的啮齿动物中脑基因表达的影响 从尤马县的农业与非农业地区，使用非靶向纳米弦和目标 QRT-PCR方法；目标2）评估混合金属暴露对啮齿动物中脑代谢谱的影响 从这两个暴露区域中，使用液相色谱 - 离子迁移率质量质谱法； 目的3）在可可菌部落土地上收集埃里科菌样品以进行初步暴露风险 评估。该项目将提供有关接触金属的神经系统影响的信息 农业和帮助开发模型，以评估服务不足的人群的健康影响 尤马县的农场工人和部落成员。