ENVIRONMENTALLY INDUCED ALTERATIONS IN NEURON AND GLIA DEVELOPMENT

在神经系统的发育过程中， 基因表达的时间和空间调节是一个关键 神经和神经胶质生长、发育和 互动。这些时间紧迫的事件被假定为 在发展中的差异磁化率的主要组成部分 有机体对环境的侮辱。这个项目考察了这些影响 各种环保剂(例如，醋酸铅、三乙基锡、 三甲基锡、甲基汞、汞蒸气和电磁 FIELDS和AIDS治疗学)，关于神经质的发展 由时空表达的变化所指示的系统 与发育调节相关的各种蛋白的mRNA的表达 具有不同的发育过程(例如，神经元迁移， 轴突延伸、突触形成和髓鞘形成)。我们有 研究表明，醋酸铅改变发育调节的结构 蛋白质。正在进行的研究正在检查信使核糖核酸 神经营养因子和蛋白质与轴突延长和 突触形成进一步了解隐蔽导联诱导的 神经网络形成过程中的变化。使用RNase 保护分析，我们已经展示了一个本体论配置文件 不同脑组织中的促炎性细胞因子和神经营养因子 地区。醋酸铅降低肿瘤坏死相关基因水平 血管内皮细胞因子α(TNFa)和白介素1α(IL-1a)的表达 同时保持神经营养因子不变。 发育期汞蒸气暴露降低了TNFa、TNFβ、 和IL-6在出生后14天的小脑中的表达，而在出生后14天 神经营养因子。这项技术正在通过 检测蛋白质信使核糖核酸水平的新探针装置的建立 与大脑的不同细胞类型和阶段相关 发展。体外实验表明，神经胶质细胞培养可以 表现出对缺血性损伤易感性的成熟模式 类似于在体内看到的低氧诱导的上调 年轻细胞中神经营养因子的mRNA在 成熟。未来研究：我们将继续创造 促炎症神经营养因子的发育概况 脑组织中的细胞因子和结构相关蛋白 暴露于已知的发育神经毒物以评估 用这种方法确定发展性的可行性 一种化学物质的神经毒性潜力，并进一步了解 这些关键时间事件的相互依存性 神经网络的形成。

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 examines the effects of various environmental agents, (e.g. lead acetate, triethyltin, trimethyltin, methyl mercury, mercury vapors, and electromagnetic fields, and AIDs therapeutics), on the development of the nervous system as indicated by alterations in the spatio-temporal expression of mRNA for various developmentally regulated proteins associated with distinct processes of development (e.g., neuronal migration, neurite extension, synapse formation, and myelination). We have shown that lead acetate alters developmentally regulated structural proteins. Ongoing studies are examining the mRNA for neurotrophins and proteins associated with axonal elongation and synapse formation to further understand the subtle lead induced alteration in the formation of the neural network. Using RNase protection assays we have demonstrated a ontological profile for pro-inflammatory cytokines and neurotrophins in various brain regions. Lead acetate decreased mRNA levels for tumor necrosis factor alpha (TNFa) and interleukin-1 alpha (IL-1a) in the cerebellum while leaving the neurotrophins unchanged. Developmental mercury vapor exposure decreased TNFa, TNFbeta, and IL-6 in the cerebellum at postnatal day 14 with no alterations in the neurotrophins. 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. In vitro experiments have shown glial cell cultures to demonstrate a maturation pattern of susceptibility to ischemic injury similar to that seen in vivo with a hypoxia-induced up-regulation of mRNA for neurotrophins in young cells that is gradually lost during maturation. Future Research: We will continue to generate developmental profiles for the neurotrophins, pro-inflammatory cytokines, and structural related proteins in brain regions following exposure to known developmental neurotoxicants to assess the feasibility of using this approach to determine developmental neurotoxic potential of a chemical and to further understand the nature of the interdependency of these critically timed events in the formation of the neural network.