ENVIRONMENTALLY INDUCED ALTERATIONS IN NEURON AND GLIA DEVELOPMENT

在神经系统发育过程中，基因表达的时空调控是神经和神经胶质细胞生长、发育和相互作用的重要组成部分。这些关键的时间事件被认为是发育中的有机体对环境胁迫的差异敏感性的主要组成部分。本项目研究了NS发育过程中的化学诱导扰动，其表明与不同的发育过程相关的各种发育调节蛋白的mRNA的时空表达的变化。我们通过核糖核酸酶保护分析表明，醋酸铅改变了大鼠神经元和胶质细胞发育调节的结构蛋白，以及凋亡基因和脑源性神经营养因子的上调。早期暴露在汞蒸气中也会提高细胞凋亡因子的信使核糖核酸水平，这与先前关于汞诱导脑细胞凋亡的报道一致。随着新探针组的建立，这项技术正在扩展，以检测与大脑发育的不同细胞类型和阶段相关的蛋白质的信使核糖核酸水平。未来研究：将检查扰乱甲状腺激素水平的化学物质PTU和二恶英的发育相关影响，以确定与神经系统结构变化的任何关系。其他研究是基于早产时发生的与缺氧缺血相关的事件。这些研究将检测白介素6对出生后早期发育的中枢神经系统的急性毒性，以及皮质神经元网络发育的分子标志物在正常个体发育中的变化。

During the development of the nervous system, the temporal and spatial regulation of gene expression is a critical component of neural and glial growth, development, and interactions. These critically timed events are assummed to be a major component in the differential susceptibility of the developing organism to environmental insult.This project examined chemical induced perturbations during development of the NS as indicated by alterations in the spatio-temporal expression of mRNA for various developmentally regulated proteins associated with distinct processes of development. We have shown by RNase protection assays that lead acetate alters developmentally regulated structural proteins for neurons and glia in the rat as well as an upregulation of apoptosis genes and brain derived neurotrophic factors. Early exposure to mercury vapors also elevate mRNA levels for apoptosis factors consistent with previous reports of mercury induced apoptosis in the brain.This technique is being expanded with the establishment of new probe sets to detect mRNA levels for proteins associated with the various cell types and stages of brain development. Future Research: The developmental related effects of chemicals which disrupt thyroid hormone levels,PTU and dioxin, will be examined to determine any relationship with structural alterations in the nervous system. Additional studies are based upon events associated with hypoxia-ischemia occurring at preterm birth. These studies will examine the acute toxicity of interleukin 6 on the early post-natal developing CNS and alteration in the normal ontogeny of molecular markers for cortical neuronal network development.