ORGANOPHOSPHATE NEUROTOXICITY IN EARLY ZEBRAFISH DEVELOPMENT

University Of Montana, Missoula MT

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Abstract

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. Organophosphate pesticides (OPs) are environmental toxins known to inhibit the catalytic activity of acetylcholinesterase (AChE). Developmental exposure to OPs has been hypothesized to disrupt other non-cholinergic pathways in the embryo, such as axon path finding, that lead to locomotion and cognition deficits in young children. In order to understand the neurological pathways affected by OP exposure in the developing vertebrate embryo, we have developed a subacute model of OP developmental exposure in zebrafish. Exposing embryos to a dose of chlorpyrifos oxon (CPO) that is non-lethal allows us to look at potential non-AChE related responses during early embryonic development. Our central hypothesis is that developmental CPO exposure results in changes in axon pathfinding in the developing CNS. The long-term goal of this project is to identify the cellular proteins that CPO modifies that result in the cognitive and locomotion deficits observed in human children who have been exposed to OP.