Superfund Research Program
Zebrafish as a Detector and Discriminator of Organophosphate Exposure
Project Leaders: Elwood A. Linney (Duke University Medical Center), Richard T. Di Giulio
Grant Number: P42ES010356
Funding Period: 2000-2011
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Progress Reports
Year: 2008 2007 2006 2005 2004 2003 2002 2001 2000
Dr. Elwood Linney’s work is based upon the hypothesis that early challenge of the embryonic nervous system with compounds that affect neuronal activity will have resulting learning/behavioral changes upon the adult. The research group’s superfund work with chlorpyrifos helped to develop this hypothesis. In this past year they have looked more closely at the nature of the organophosphate chlorpyrifos (commercial name Dursban) effects upon the early embryo. In collaboration with Dr. Levin's laboratory the group is narrowing in on a vulnerable window of exposure for adult effects to occur. That collaboration has also allowed them to identify changes in certain neurotransmitter levels in larvae and adults after embryonic chlorpyrifos exposure. These are valuable clues and should allow them to follow up what the immediate and possibly long-term effects of the early exposure is on the developing nervous system.
As an independent test of the hypothesis the researchers are also challenging the early embryo with the organochlorine dieldrin. This compound appears to have a different and earlier vulnerable window for zebrafish embryos. This second challenge is currently in a more developmental stage and will require larval and adult behavioral evaluations.
As a relatively new technological approach to mechanism of these exposure effects, they have been making transgenic lines of zebrafish that have light-activateable ion channels or pumps expressing in parts of the nervous system. This should allow the group to activate or repress neural activity in selected neurons to determine if they can reproduce the effects of these environmental compounds upon eventual, adult behavior. Since bathing an embryo in a environmental toxicant can have primary, secondary and tertiary effects, the researchers suspect that this new technological approach might allow them to more efficiently determine mechanism and targets of environmental toxicants upon the developing, embryonic nervous system.