Effect of Lead, Manganese and Stress During Development

开发过程中铅、锰和应力的影响

• 批准号: 7282314
• 负责人: MICHAEL T WILLIAMS
• 金额: $ 34.35万
• 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/7282314
• 关键词: animal developmental psychology; behavior disorders; behavior test; behavioral /social science research tag; child behavior disorders; cognition disorders; developmental neurobiology; disease /disorder model; early experience; embryo /fetus toxicology; environmental exposure; hypothalamic pituitary adrenal axis; isolation /deprivation; laboratory rat; lead; learning disorders; magnetic resonance imaging; manganese; neuropathology; neurotoxicology; psychological stressor; social space; stress

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。暴露于低水平的各种神经毒素已被建议 作为这些变化的潜在因素。例如，已知低水平的铅与 学习缺陷和社会行为问题。动物模型的一个问题是， 神经毒素的另一个问题是，即使人类接触到这种毒素， 以及许多其他环境因素。例如，已知存在差异暴露 低社会经济地位家庭中的重金属。因此，我们将研究铅的影响 和锰（因为已知锰会增强铅含量的增加， 在大脑中积累）与压力源（隔离，过度拥挤，或有限的资源， 母亲抑郁症）来模仿人类的状况。第一个目标是确定哪种压力源具有 通过测量生理参数， 给药以及研究这种组合对神经递质和 长期电位诱导。第二个目的是研究铅或 锰与对动物学习能力和社交方面的压力相结合。我们将 使用一种新的方法来研究这些动物的学习和记忆， 测试不同类型学习的学习测试。这与人类如何学习有关， 好.这一目标将为建立低水平暴露模型和了解功能性 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。 与人类学习记忆和社会行为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MRI以及观察动物成年后的神经生理反应。这些 研究将提供急需的数据，说明神经毒素与 环境相关的压力源。潜在的机制将通过研究神经递质来探索 神经内分泌系统和谷氨酸受体复合物。