Effect of Lead, Manganese and Stress During Development

开发过程中铅、锰和应力的影响

• 批准号: 7447456
• 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/7447456
• 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; Condition; Corticosterone; Corticotropin; Corticotropin-Releasing Hormone; Country; DLG4 gene; Daily; Data; Dependency; Development; Disruption; 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; Mental Depression; Metal exposure; Modeling; Mothers; Neuraxis; Neurobiology; Neuronal Injury; Neurosecretory Systems; Neurotoxins; Neurotransmitters; Numbers; Outcome; Output; Paint; Parents; Physiological; Pituitary Gland; Poverty; Principal Investigator; Problem behavior; Proteins; Research Personnel; Resources; Score; Social Behavior; Social Interaction; Stress; Study models; Testing; Thinking; Time; Toxic Environmental Substances; Water; anti social; base; behavior test; cohort; critical developmental period; day; depressive symptoms; deprivation; design; 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; postnatal; programs; 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正在稳步上升，但其病因 这些行为变化是未知的。建议接触低水平的各种神经毒素 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关于各种因素的影响 神经毒素的一个缺点是，即使发生人类接触，它们也仅限于研究一个因素 以及许多其他环境因素。例如，已知存在差异曝光 社会经济地位低的家庭对重金属的影响。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，从而导致铅含量增加） 累积在大脑中）与压力源（孤立、过度拥挤或资源有限）相结合 母亲抑郁症）来模仿人类的状况。第一个目标是确定哪个压力源具有 通过测量生理参数对重金属暴露影响最大 管理以及研究这种组合对神经递质和的长期影响 长时程增强诱导。第二个目的是研究铅或铅的剂量依赖性。 锰与对动物的学习能力和社会方面的压力相结合。我们将会 使用一种新颖的方法来研究这些动物的学习和记忆，结合使用 测试不同类型学习的学习测试。这与人类如何学习有关 出色地。这一目标将为模拟低水平暴露和理解功能提供基础。 发生的变化。第三个目标是将铅、锰和应力结合起来并评估其影响 与人类学习记忆和社会行为的接触更加相关的组合。最后的目标 旨在调查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 研究将提供急需的关于神经毒素与神经毒素结合的低水平影响的数据 环境相关的压力源。将通过研究神经递质来探索潜在机制 以及神经内分泌系统和谷氨酸受体复合物。