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: 10312899
• 负责人: JONATHAN M CREDO
• 金额: $ 3.86万
• 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/10312899
• 关键词: Neurological; effects; toxic; metal; exposure

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，提供超过90%的冬季绿叶蔬菜 为了保持高农业产量，美国每年需要超过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接触源， 化学品的居民，特别是移民和季节性农场工人和那些住在附近的农业 之地以前的研究集中在有机农药和铅暴露源，但无机 在这一领域尚未对金属基农药进行审查。我做了定量金属（loid）分析 人（n = 323）和啮齿动物（Peromyscus eremicus，n = 300）毛发样本， 神经毒性金属（特别是铜和锰）的水平已知与不利的健康结果。 在这些发现之后，初步的转录组学分析表明遗传途径被破坏， 包括那些与脂质代谢和肌肉收缩有关的蛋白质， 从尤马州农业区和非农业区捕获的地雷。Cu和Mn是 天然存在的元素，是酶反应中必需的微量营养素，但两者在高温下都是有毒的。 浓度的Cu引起组织中的非特异性氧化损伤，而Mn在基底膜中积累。 神经节和多巴胺能神经元，并与儿童的行为问题和运动功能障碍有关， 成年人了农业化学品使用量高的农业地区附近的农场工人和社区是一个 对人群过度接触铜和锰的研究不足。这一建议扩大了我的 初步工作，确定了铜和锰浓度升高的人类和啮齿动物的头发收集， 尤马县通过使用P. eremicus啮齿动物模型研究转录组学和脂质组学反应， exposure.此外，我正在与尤马的Cocopah部落合作制定类似的办法 县评估污染物暴露在他们的人的风险。在多学科的指导下， 目的1）评估混合金属暴露对啮齿动物大脑基因表达的影响， 尤马县的农业区与非农业区，使用非靶向Nanostring和靶向Nanostring qRT-PCR方法;目的2）评估混合金属暴露对啮齿动物脑代谢谱的影响 从这两个曝光区域，使用液相色谱-离子迁移谱-质谱; 和目标3）在Cocopah部落土地上采集P. eremicus样本，进行初步暴露风险评估 考核该项目将提供关于接触用于治疗癌症的金属对神经系统的影响的信息。 农业和援助开发模型，评估对服务不足人口的健康影响， 农场工人和部落成员在尤马县。