Effect of Lead, Manganese and Stress During Development

开发过程中铅、锰和应力的影响

• 批准号: 7632166
• 负责人: MICHAEL T WILLIAMS
• 金额: $ 35.68万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-18 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7632166
• 关键词: Address; Adolescence; Adrenal Glands; Adult; Affect; Animal Model; Animals; Attention; Attention deficit hyperactivity disorder; Behavior; Behavioral; Blood - brain barrier anatomy; Brain; Child; Cognitive; Cognitive deficits; Complex; Corticosterone; Corticotropin; Corticotropin-Releasing Hormone; Country; DLG4 gene; Data; Dependency; Development; Dose; Economics; Environment; Environmental Risk Factor; Etiology; Excision; Exposure to; Family; Fibrinogen; Floor; Foundations; Gasoline; Genetic Crossing Over; Glutamate Receptor; Half-Life; Heavy Metals; Hippocampus (Brain); Homeostasis; Hour; Household; Human; Hydrocortisone; Hyperactive behavior; Hypothalamic structure; Immunohistochemistry; Impaired cognition; Infant formula; Juvenile Delinquency; Lead; Learning; Left; Life; Life Cycle Stages; Link; Litter Size; Locomotion; Long-Term Effects; Long-Term Potentiation; Magnetic Resonance Imaging; Manganese; Measures; Memory; Metal exposure; Modeling; Mothers; Neuraxis; Neurobiology; Neuronal Injury; Neurosecretory Systems; Neurotoxins; Neurotransmitters; Outcome; Output; Paint; Parents; Physiological; Pituitary Gland; Poverty; Principal Investigator; Problem behavior; Research Personnel; Resources; Social Behavior; Social Interaction; Stress; Study models; Testing; Time; Toxic Environmental Substances; Water; anti social; base; behavior test; cohort; critical period; depression; depressive symptoms; deprivation; design; emerging adult; exposed human population; feeding; gray matter; hypothalamic-pituitary-adrenal axis; indexing; lead exposure; maternal depression; maternal stress; mature animal; monoamine; morris water maze; neglect; neurochemistry; neurodevelopment; neurophysiology; novel strategies; offspring; postnatal; programs; protein complex; research study; response; sex; social; soy; stressor

Learning and behavior problems among US children appear to be rising steadily, however the etiology for these behavioral changes is unknown. Exposure to low-levels of various neurotoxins has been suggested as a potential factor in these changes. For example, low levels of lead are known to be associated with learning deficits and social behavior problems. One issue with animal models for the effects of various neurotoxins is that they are limited to investigating only one factor even though human exposures occur together with many other environmental factors. For example, it is known that there is a differential exposure to heavy metals in low social economic status households. Therefore, we will investigate the effects of lead and manganese (since manganese is known to potentiate the increase in the amount of lead that accumulates in the brain) in combination with stressors (isolation, overcrowding, or limited resources with maternal depression) to mimic human conditions. The first aim is to determine which stressor has the greatest impact on heavy metal exposure by measuring physiological parameters during the period of administration as well as investigating the long-term effects of this combination on neurotransmitters and long-term potenitation induction. The second aim is to investigate the dose-dependency of lead or manganese in combination with stress on the learning ability and social aspects of the animals. We will be using a novel approach to investigating learning and memory in these animals by using a combination of learning tests that test different types of learning. This is relevant to how humans would have to learn as well. This aim will provide a foundation to model low level exposure and to understand the functional changes that occur. The third aim is to combine lead, manganese and stress and assess the impact of this more relevant combination to human exposures on learning and memory and social behavior. The last aim is designed to investigate the developmental changes that occur related to the three combination exposure by using MRI as well as looking at the nuerophysiological response when the animals are adults. These studies will provide much needed data on the low-level effects of neurotoxins in combination with environmentally relevant stressors. Potential mechanisms will be explored by investigating neurotransmitter and neuroendocrine systems and the glutamate receptor complex.

美国儿童的学习和行为问题似乎在稳步上升，然而 这些行为变化是未知的。人们建议暴露在低水平的各种神经毒素中。 作为这些变化的一个潜在因素。例如，已知低水平的铅与 学习障碍和社会行为问题。动物模型的一个问题是各种不同的 神经毒素的作用在于，即使人类接触到神经毒素，它们也仅限于研究一个因素。 再加上其他许多环境因素。例如，已知存在不同的暴露 对社会经济地位较低家庭的重金属。因此，我们将调查铅的影响 和锰(因为众所周知，锰会促进铅量的增加，从而 积聚在大脑中)与应激源(隔离、过度拥挤或资源有限)相结合 母性抑郁症)来模拟人类的情况。第一个目标是确定哪种压力源具有 通过测量期间的生理参数对重金属暴露的最大影响 以及研究这种组合对神经递质和 长期潜伏期诱导。第二个目标是研究铅或铅的剂量依赖关系 锰与压力相结合，对动物的学习能力和社会方面产生了影响。我们会的 使用一种新的方法研究这些动物的学习和记忆，方法是结合使用 测试不同类型学习的学习测试。这与人类如何学习是相关的 井。这一目标将为建立低水平暴露的模型和理解功能性 发生的变化。第三个目标是将铅、锰和压力结合起来，并评估其影响 与人类在学习和记忆以及社会行为方面的暴露更相关的组合。最后一个目标 旨在研究与三种组合暴露相关的发育变化 通过使用核磁共振以及观察动物成年后的神经生理学反应。这些 研究将提供亟需的数据，说明神经毒素与 与环境有关的压力源。将通过研究神经递质来探索潜在的机制 神经内分泌系统和谷氨酸受体复合体。