Environmentally Induced Alterations In Neuron And Glia Development and Aging

发育中的神经系统对环境因子的敏感性一直是儿童健康问题的主要关注点。 大脑中各种细胞类型之间的形成和相互作用是关键的时间事件。这种脆弱性窗口被认为是发展中的有机体对环境损害的不同敏感性的主要组成部分。该项目研究了神经系统发育过程中化学诱导的扰动，如发育中大脑的形态和分子特征的各种改变以及青春期和老年动物的相关神经行为结果所示。我们已经报道，低水平的铅暴露在出生后的发展改变了正常的发展过程中的细胞凋亡和修剪。 在研究非人类灵长类动物早期发育铅暴露的长期影响时，我们已经证明了铅暴露与海马体中淀粉样斑块形成的增加与衰老之间的关联。其他研究还审查了发育过程中接触汞的影响。 这些研究是基于自闭症患者的免疫功能改变和大脑免疫细胞（小胶质细胞）变化的报告。 在检查一个可能增加的脆弱性的发育中的大脑作为一个功能的免疫系统的改变，我们进行了广泛的研究，复制和扩展以前的工作表明乙基汞（作为硫柳汞作为一个模型的儿童疫苗接种）在自身免疫易感SJL小鼠的差异效应。 使用有针对性的特定行为任务建模自闭症，如社会行为，除了运动表现，免疫组织化学，无偏见的体视学，和汞的靶器官化学分析，我们没有发现发育暴露于乙基汞或儿童疫苗的不良影响。 我们与毒理学运营分支合作，制定了一项检测方案，以检查环境化学品的神经发育毒性，该方案可用于评价发育神经毒性相关化合物。 除了在发育过程中发生的变化外，该项目还将开发一种方法来评估早期发育暴露于环境化学品对老年大脑的潜在影响或影响。 在这些研究中，我们继续使用许多方法来检查暴露于环境因子后发育中的神经系统的变化，包括免疫组织化学，检测mRNA水平的分子技术，以及神经行为功能的评估。

The susceptibility of the developing nervous system to environmental agents has been a major concern with regard to children's health issues. The formation and interactions between the various cell types in the brain are critically timed events. Such windows of vulnerability is assummed to be a major component in the differential susceptibility of the developing organism to environmental insult. This project examines chemical induced perturbations during development of the nervous system as indicated by various alterations in the morphology and molecular profile in the developing brain and assoicated neurobehavioral outcome in adolescent and aging animals. We have reported that low-level lead exposure during post-natal development alters the normal developmental process of apoptosis and pruning. In examining the long term effect of early developmental lead exposure in the non-human primate, we have demonstrated an association between lead exposure and the increase in amyloid plaque formation in the hippocampus with aging. Additional studies have examined the effects of mercury exposure during development. These studies were based upon reports of altered immune functioning and changes in the brain immune cell, the microglia, in autistic patients. In examining a possible increased vulnerability of the developing brain as a function of an altered immune system, we have conducted an extensive study to replicate and expand previous work suggesting a differential effect of ethyl mercury (administered as thimerosal as a model of childhood vaccination) in the autoimmune prone SJL mice. Using targeted specific behavioral tasks modeling autism such as social behavior in addition to motor performance, immunohistochemistry, unbiased stereology, and target organ chemical analysis for mercury, we did not identify adverse effects of developmental exposure to ethyl mercury or childhood vaccines. Working with the Toxicology Operations Branch, we have establishing a testing protocol to examine the neurodevelopmental toxicities of environmental chemicals that can be employed in an applied manner to evaluate compounds of concern for developmental neurotoxicity. In addition to changes occurring during development, this project will also develop an approach to evaluate latent effects or effects on the aged brain as the result of early developmental exposure to environmental chemicals. For these studies we continue to use a number of methods to examine alterations in the developing nervous system following exposure to environmental agents including immunohistochemistry, molecular techniques to examine mRNA levels, as well as assessment of neurobehavioral functioning.