Environmentally Induced Alterations In Neuron And Glia D

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。虽然目前暴露于环境因子的水平并不代表急性损伤，但神经系统的破坏可能与神经网络形成和/或神经系统功能的结构改变有关。该项目的目标是开发和验证测试方法，使我们能够评估发育过程中各种类型的化学诱导的大脑扰动。大脑中各种细胞类型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育中的生物体对环境伤害的不同敏感性的主要组成部分。该项目研究了神经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这种暴露的相关神经行为结果所示。正在研究的具体项目包括：1）肌肉注射各种汞剂（包括甲基汞、乙基汞和疫苗保护剂硫柳汞）后，汞在幼龄动物大脑中的分布。2)妊娠期和出生后发育期间暴露于干扰甲状腺激素稳态维持的化合物后脑中神经元过程的改变。已知早期发育暴露于无机铅会改变大脑发育。基于我们以前的研究，检查特定的神经元和神经胶质细胞标记物低水平铅暴露后，我们开始了一项研究，以更广泛的方式检查多个神经系统特异性基因的发育个体发生使用cDNA微阵列技术。这些研究的一个具体的发现是一个特定的氯丛基因的发育模式的转变，表明氯丛的早期成熟作为一种保护机制，对重金属暴露，然而，这种早期成熟的后果还有待研究。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. While current exposure levels to environmental agents does not represent an acute injury, disruption to the nervous system may be associated with either a structural alteration in the formation of the neural network and/or in nervous system functioning. It is the goal of this project to develop and validate test methods that will allow us to assess various types of chemical-induced perturbations of the brain during development. 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 nevous as indicated by various alterations in the morphology and molecular profile in the developing brain and assoicated neurobehavioral outcome of such exposure. The specific projects under study include 1) distribution of mercury to the brain of young animals following the intramuscular injection of various mercuricals including methylmercury, ethylmercury and the vaccine perservative, thimerosal. 2) Alterations in neuronal processes in the brain following exposure to compounds that perturb homeostatic maintenance of thyroid hormone during gestational and postnatal development. Early developmental exposure to inorganic lead is known to alter brain development. Based upon our previous studies examining specific neuronal and glia markers following low level lead exposure we initiated a study to examine in a more broad manner the developmental ontogeny of multiple nervous system specific genes using cDNA microarray techniques. One specific finding of these studies was the shift in the developmental pattern for a specific chlorid plexus gene suggesting an early maturation of the chlorid plexus as a protective mechanism against a heavy metal exposure however, the consequences to such an early maturation is yet to be studied. 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.