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