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

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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.