THE EFFECTS OF EARLY EMBRYONIC EXPOSURE TO PCBS ON THE DEVELOPING NERVOUS SYSTEM

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该提案描述了一系列使用斑马鱼的实验，这些实验将确定早期胚胎暴露于多氯联苯对神经发育的影响。一个多层次的一套检测将被用来描述胚胎暴露于环境相关浓度的Aroclor 1254，共面和非共面多氯联苯的混合物的神经发育影响。我们实验室的初步研究表明，six 3b表达的变化可能在PCB暴露的神经影响中很重要。 这种潜在的基因靶标的作用，以及通过微阵列分析鉴定的其他基因，将通过真实的时间PCR来验证。将通过原位杂交进行基因表达变化的定位。我们将专门寻找发育中大脑基因表达的变化。对大脑结构和单个神经元的分析将记录多氯联苯对中枢神经系统的具体影响。我们将使用Cave自动化虚拟环境来准确识别大脑和单个神经元的三维结构的变化。Cave是一个8 'x8'x8'的房间，共焦数据集的3D重建以立体方式投影在地板和墙壁上。在立体投影环境中， 由于用户更好的深度感知，对特定结构的理解得到了改善。这项研究将首次使用Cave来确定神经结构的变化。这些研究提供了一种独特的方法，可以在从分子机制到总体发育影响的分析水平上研究PCB暴露对神经发育的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This proposal describes a series of experiments using zebrafish that will identify neurodevelopmental effects of early embryonic exposure to PCBs. A multilevel set of assays will be used to describe the neurodevelopmental effects of embryonic exposure to environmentally relevant concentrations of Aroclor 1254, a mixture of coplanar and non-coplanar PCBs. Preliminary research in our laboratory suggests that changes in expression of six3b may be important in the neurological effects of PCB exposure. The role of this potential gene target, as well as other genes identified by microarray analysis, will be verified by real time PCR. Localization of the changes in gene expression will be done by in situ hybridization. We will specifically look for changes in gene expression in the developing brain. Analysis of the brain structure and individual neurons will document specific effects of PCBs on the central nervous system. We will use a Cave automated virtual environment to accurately identify the changes in the 3-dimensional structure of the brain and individual neurons. The Cave is an 8'x8'x8' room in which the 3-D reconstruction of confocal datasets is projected in stereo on the floor and walls. In the stereoscopically projected environment the understanding of specific structures is improved due to better depth perception by the user. This study will be the first to use a Cave to determine changes in neurological structure. These studies provide a unique approach where the neurodevelopmental effects of PCB exposure can be investigated at levels of analysis ranging from molecular mechanisms to gross developmental effects.