The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 2007-2008

Zebrafish as an in vivo model system for identifying developmental neurotoxicants

Pamela Lein, PhD
Oregon Health & Science University

There is evidence that exposure of the developing human nervous system to toxic chemicals can cause changes in the behavioral, emotional and intellectual function of children.  There is, therefore, much interest in screening chemicals to identify those with potential to cause developmental neurotoxicity.  Tests currently approved for this purpose primarily use rodents and are complex and expensive in terms of scientific resources, time and animal use. We propose to evaluate the zebrafish as an alternative model for screening chemicals for possible adverse effects on the developing brain.  We will use a specific transgenic line of zebrafish (NBT-GFP) in which motor neurons express green fluorescent protein (GFP) to measure axon outgrowth and quantify motor behavior at varying times following exposure to a panel of toxicants generally regarded as neurotoxic.  The reasons for choosing the zebrafish include:  (1) The cell and molecular mechanisms that control the normal development of the zebrafish nervous system are remarkably similar to those in humans, increasing the validity of using this model to assess potential risks to the developing human nervous system.  (2) The expression of green fluorescent protein (GFP) in specific populations of zebrafish neurons coupled with the fact that zebrafish are transparent, allows non-invasive imaging of these GFP-labeled neurons in the same animal over time, thereby significantly reducing the number of animals required for developmental neurotoxicity testing.  (3) The small size, rapid nervous system development and short life cycle of zebrafish are favorable for adapting this model system for testing large numbers of chemicals.