Developmental Effects of Manganese Exposure in Rural Adolescents: The CARES Cohort Comes of Age

农村青少年接触锰对发育的影响：CARES 群体的成年

• 批准号: 9927019
• 负责人: Kim M Cecil
• 金额: $ 59.16万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9927019
• 关键词: Achievement; Address; Adolescence; Adolescent; Air; Anatomy; Apoptosis; Attention; Axonal Transport; Basal Ganglia; Behavior; Biliary; Biological Markers; Blood; Brain; Bypass; Cerebellum; Child; Chronic; Cognition; Cohort Studies; Communities; Deposition; Development; Diagnosis; Diffusion; Dose; Elements; Emotional; Environmental Risk Factor; Environmental Tobacco Smoke; Event; Excretory function; Exhibits; Exposure to; Follow-Up Studies; Gait; Gasoline; Globus Pallidus; Growth; Growth and Development function; Health; Infant; Ingestion; Inhalation; Lead; Longitudinal cohort study; Magnetic Resonance Imaging; Manganese; Measures; Metabolism; Methodology; Methods; Minerals; Motor; Multimodal Imaging; Musculoskeletal Equilibrium; Neuraxis; Neuroanatomy; Neuropsychology; Neurosciences; Neurotoxins; Nose; Nutrient; Ohio; Outcome; Parkinson Disease; Pathway interactions; Pattern; Pediatric cohort; Physicians; Physiology; Play; Policies; Population; Prefrontal Cortex; Process; Protocols documentation; Psyche structure; Reaction Time; Research; Risk; Risk-Taking; Role; Rural; Rural Appalachia; Source; Structure; Structure of subthalamic nucleus; Substantia nigra structure; United States; Work; adverse outcome; base; cognitive function; cohort; executive function; frontal lobe; high risk; imaging modality; innovation; myelination; nervous system development; neurobehavior; neurodevelopment; neuroimaging; neurotoxic; neurotoxicity; novel; olfactory bulb; putamen; relating to nervous system; response; spectroscopic imaging; synaptogenesis; white matter

Manganese (Mn) plays an essential role in normal growth and development; however, overexposure to Mn can result in neurotoxicity. This dual role of Mn as essential mineral and neurotoxicant appears as a biphasic dose-response curve for neurodevelopmental health outcomes in children. Children may be particularly susceptible to the neurotoxic effects of ambient Mn exposure, as their brains are undergoing a dynamic process of growth, differentiation, pathway direction, and apoptosis, all of which can be influenced by environmental factors. Recent developments in magnetic resonance imaging (MRI) and spectroscopy (MRS) can provide novel, quantitative information about the effects of Mn on brain anatomy and physiology; yet these imaging methods have never been applied to an adolescent population exposed to chronic ambient Mn. Given the role of Mn as both nutrient and neurotoxicant, we anticipate that biomarkers of Mn exposure will exhibit a biphasic dose- response association with adolescent neurobehavior, neuromotor function, brain anatomy and physiology, and hypothesize that both low (1st quartile) and high (4th quartile) levels of exposure will be significantly associated with deficits in these domains. This overarching hypothesis will be addressed through two specific aims. Specific Aim 1: Evaluate neurodevelopment with historic and current biomarkers of Mn in a cohort of rural adolescents in order to evaluate the impact of Mn from essential to excess on executive function, attention and reaction time, cognition, achievement, behavior, and neuromotor status. Specific Aim 2: Conduct a sub-study of adolescents based on previously determined Mn biomarkers using quantitative MRI/S in order to evaluate the effects of Mn exposure from essential to excess on neuroanatomy, metabolism, organization, function and connectivity. Neuroimaging outcomes (volume, metabolite concentrations, metrics for diffusion tensor, functional activation, and network connectivity) will be compared with historic and current biomarkers of Mn. This well-characterized longitudinal cohort study of adolescents will advance our understanding of the impact of Mn on neurodevelopment, and brain anatomy and physiology using innovative MRI methodologies. These patterns may be useful in defining the lines of essential benefit and neurotoxicological harm from Mn. The findings from this study will have regional, national and global implications for advancement of neuroscience and will be used to inform policy related to Mn in gasoline and ambient air standards. This proposal leverages the only cohort available in the United States that can directly address these aims.

锰（MN）在正常生长和发育中起着至关重要的作用。然而， 过度暴露于MN会导致神经毒性。 MN作为必不可少的矿物和 神经毒性作为神经发育健康的双相剂量响应曲线出现 儿童的结果。儿童可能特别容易受到神经毒性的影响 环境MN暴露，因为他们的大脑正在经历动态的增长过程， 分化，途径方向和凋亡，所有这些都可以受到影响 环境因素。磁共振成像（MRI）和 光谱法（MRS）可以提供有关MN对大脑影响的新颖的定量信息 解剖学和生理学；然而，这些成像方法从未应用于青少年 暴露于慢性环境MN的人群。鉴于MN作为营养和 神经毒性，我们预计MN暴露的生物标志物将表现出双相剂量 - 与青少年神经行为，神经运动功能，大脑的响应关联 解剖学和生理学，并假设低（第一四分之一）和高（第4个） 四分位数）暴露水平将与这些缺陷显着相关 域。这个总体假设将通过两个具体目标解决。 特定目的1：用MN的历史和当前生物标志物评估神经发育 为了评估MN从本质到过量对MN的影响 执行功能，注意力和反应时间，认知，成就，行为以及 神经运动状态。特定目标2：基于以前的青少年进行子研究 使用定量MRI/S确定MN生物标志物，以评估MN的影响 从基本到过度的神经解剖学，代谢，组织，功能和 连接性。神经影像学结果（体积，代谢物浓度，扩散指标 张量，功能激活和网络连接性将与历史和 当前的生物标志物。这项对青少年的纵向纵向队列研究将 促进我们对MN对神经发育以及脑解剖结构的影响以及 使用创新MRI方法的生理学。这些模式可能对定义 MN的基本益处和神经毒理学伤害的线。这项研究的发现将 对神经科学的发展具有区域性，民族和全球影响，将是 用于为与MN有关的汽油和环境空气标准的政策提供信息。这个建议 利用美国唯一可以直接解决这些目标的人群。