Stress-Lead Interactions and Child Development

压力导致的相互作用和儿童发展

基本信息

批准号：
8432556
负责人：
Robert O Wright
金额：
$ 36.46万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-01-15 至 2015-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8432556
关键词：
Ablation Address Age Animal Experimentation Animal Experiments Animal Testing Animals Attention Behavior Behavioral Biological Markers Birth Blood Budgets California Chemicals Child Child Development Childhood Cities Clinical Cohort Studies Collaborations Coupled Coupling DNA Data Decision Making Dental Dental Enamel Dentin Development Elements Epidemiologic Studies Epidemiology Epigenetic Process Exposure to Freezing Future Growth Hair Human Intervention Joints Lasers Lead Lead Poisoning Life Link Manganese Mass Spectrum Analysis Measures Memory Metal exposure Metals Methodology Methods Mexico Modeling Neurologic Neurotoxins Neurotransmitters Observational Study Parents Pathologic Performance Perinatal Exposure Plasma Policies Pregnancy Trimesters Procedures Public Health Public Policy RNA Radial Reaction Time Research Research Personnel Resolution Rodent Model Role Staging Stress Techniques Testing Time Tissues Tooth structure Toxic effect Toxicology Translational Research Translations Urine Variant Visit Visuospatial Work arm biobank cohort computerized deciduous tooth design executive function exposed human population infancy information processing interdisciplinary collaboration lead exposure neurodevelopment neuropathology neuropsychiatry neurotoxic neurotoxicity neurotoxicology performance tests postnatal prenatal prevent programs prospective public health relevance randomized trial response social stressor virtual visual information visual learning

项目摘要

DESCRIPTION (provided by applicant): Manganese (Mn) is an emerging neurotoxicant. Two critical issues in the neurotoxicology of Mn include the 1) extrapolation of animal results to humans, and 2) limitations in defining/assessing critical exposure windows in epidemiologic studies. Because randomized trials cannot be conducted for neurotoxic agents, research translation in neurotoxicology involves epidemiologic observational studies that rely on parallel research in animals to determine mechanisms of action. However, such studies seldom measure the same functional domtheains or address exposures at the same life stages, at least not in a coordinated fashion. Although there are several caveats when extrapolating results from animals to humans, one caveat, the use of different neurophenotypes, can now be overcome, given the development of computerized tests of animal/human behavior, such as the virtual radial arm maze and temporal response differentiation test (a fixed interval response). The investigators will employ these tests and others in children in parallel to conducting animal toxicology studies that also address Mn exposure in specific life stages. Their team has also developed a method to reconstruct past Mn exposure using deciduous teeth that expands upon prior work by measuring Mn in specific growth rings corresponding to discrete life stages. In effect, the investigators can now reconstruct past exposure to Mn at multiple developmental windows, a technique that may even be superior to prospective blood Mn levels. In this supplement, the investigators will leverage an ongoing cohort study in Mexico City to assess Mn exposure and child neurodevelopment, while tightly coupling our findings to animal toxicology studies measuring the same neurophenotypes. This ViCTER application is a new transdisciplinary collaboration among investigators with expertise in animal toxicology (Smith) and manganese epidemiology/exposure assessment (Lucchini/Arora), bringing them together to form a unique virtual consortium to study Mn toxicity in children.

描述（由申请人提供）：锰（MN）是一种新兴的神经毒性。 MN神经毒理学的两个关键问题包括1）动物结果向人类推断，以及2）在流行病学研究中定义/评估关键暴露窗口的局限性。由于无法针对神经毒性剂进行随机试验，因此神经毒理学的研究翻译涉及流行病学观察性研究，这些研究依赖于动物的平行研究来确定作用机理。但是，这样的研究很少衡量相同的功能性Domtheains或在相同的生活阶段解决暴露，至少没有以协调的方式进行暴露。尽管在将动物从动物到人类推断出的结果时有几个警告，但考虑到动物/人类行为的计算机化测试的发展，一个警告现在可以克服不同的神经表现型，例如虚拟径向臂迷宫和暂时响应分化测试（固定间隔响应）。研究人员将在儿童中采用这些测试，并在进行动物毒理学研究并行解决MN在特定生命阶段的暴露。他们的团队还开发了一种使用落叶牙齿来重建过去MN暴露的方法，该牙齿通过测量与离散生命阶段相对应的特定生长环中的MN来扩展先前的工作。实际上，研究人员现在可以在多个发育窗口中重建过去对MN的接触，该技术甚至可能优于预期的血液MN水平。在这种补充剂中，研究人员将利用一项在墨西哥城正在进行的队列研究来评估MN暴露和儿童神经发育，同时将我们的发现与测量相同神经表现的动物毒理学研究紧密耦合。该Victer应用程序是在动物毒理学（Smith）和锰流行病学/暴露评估（Lucchini/Arora）方面具有专业知识的研究人员之间的新跨学科合作，使他们聚集在一起，形成了一个独特的虚拟财团来研究儿童的MN毒性。