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

早期胚胎接触 PCB 对神经系统发育的影响

• 批准号: 7725164
• 负责人: Jill Kreiling
• 金额: $ 3.11万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725164
• 关键词: 3-Dimensional; Aroclor 1254; Biological Assay; Brain; Computer Retrieval of Information on Scientific Projects Database; Data Set; Depth Perception; Development; Embryo; Environment; Exposure to; Floor; Funding; Gene Expression; Gene Targeting; Genes; Grant; In Situ Hybridization; Individual; Institution; Laboratories; Microarray Analysis; Molecular; Nervous system structure; Neuraxis; Neurologic; Neurons; Polychlorinated Biphenyls; Polymerase Chain Reaction; Range; Research; Research Personnel; Resources; Role; Series; Source; Structure; Time; United States National Institutes of Health; Zebrafish; improved; reconstruction; research study; three dimensional structure; virtual

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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项建议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。将使用一套多水平的分析方法来描述胚胎暴露于与环境相关的Aroclor 1254浓度的神经发育影响，Aroclor 1254是共面和非共面多氯联苯的混合物。我们实验室的初步研究表明，Six3b表达的变化可能在多氯联苯暴露的神经效应中起重要作用。这个潜在的基因靶点以及通过微阵列分析确定的其他基因的作用将通过实时荧光聚合酶链式反应来验证。基因表达变化的定位将通过原位杂交进行。我们将专门寻找发育中大脑中基因表达的变化。对大脑结构和单个神经元的分析将证明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。洞穴是一个8‘x8’x8‘的房间，共焦数据集的3-D重建在地板和墙壁上以立体投影。在立体投影环境中， 由于用户对深度的感知更好，因此对特定结构的理解得到了改进。这项研究将是第一次使用洞穴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多氯联苯暴露对神经发育的影响。