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生物体对环境侮辱的不同易感性的主要组成部分。该项目通过与不同发育过程相关的各种发育调节蛋白mRNA的时空表达变化，研究了NS发育过程中化学诱导的扰动。我们已经通过RNase保护实验表明，醋酸铅改变了大鼠神经元和神经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。早期暴露于汞蒸气也会升高凋亡因子mRNA水平，这与先前关于汞诱导脑细胞凋亡的报道一致。随着新的探针组的建立，这项技术正在得到扩展，以检测与各种细胞类型和大脑发育阶段相关的蛋白质的mRNA水平。未来研究：将研究扰乱甲状腺激素水平的化学物质（PTU和二恶英）对发育的影响，以确定其与神经系统结构改变的关系。其他的研究是基于与早产时发生的缺氧缺血相关的事件。这些研究将研究白细胞介素6对出生后早期中枢神经系统发育的急性毒性，以及皮质神经元网络发育的分子标志物正常个体发生的改变。-小鼠，大鼠，大脑，发育，醋酸铅，汞蒸气，缺氧

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 assumed 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. - mouse, rat, brain, development, lead acetate, mercury vapors, hypoxia