The Neural and Behavioral Toxicity Assessment (NBTA) Core will provide information concerning the cellular and neurobehavioral consequences of toxicant exposures being studied in our Superfund Center. Neurotoxicant actions will be evaluated by cell-based screening using neuronotypic PC12 cells, neural stem cells, and neuronal-glial co-cultures, to screen for developmental neurotoxicity across the entire spectrum of neurodevelopmental events, from cell replication to differentiation into specific neural and neurotransmitter phenotypes. This will provide comparative dose-effect relationships for related chemicals in each study, beneficial or harmful consequences of remediation strategies, and information on potential additive or synergistic toxic effects. The neurobehavioral screen will provide detailed assessment of cognitive and emotional functions affected by developmental toxicant exposures in test batteries that we have designed for the diverse models studied within the Center. The neurobehavioral batteries are tailored to the rodent and fish model systems used in the Center. These complementary models will be used to help the projects determine how the toxicant-induced molecular events, neurochemical disruption and neurocircuit miswiring cause persistent functional behavioral impairment. Specifically, for each project, the NBTA Core will include delineation of neurotransmitter systems and neuronal projections involved in the functional defects, as well as potential amelioration of toxicant-induced impairment as a result of different remediation strategies. The NBTA Core interacts with every project within the Center and provides a translation from the basic mechanistic studies of the individual projects to the potential impact on functional outcomes involving nervous system dysfunction. By providing a standardized approach to toxicity assessment, this core ensures that each of the projects and models shares common approaches to mechanism and outcome.

Public Health Relevance

The Neural and Behavioral Toxicity Assessment (NBTA) Core will provide service to all Projects. The in vitro tests will provide rapid assessment of cellular toxicity of the chemicals under study. The neurobehavioral tests will provide functional information concerning effects of the toxicants on cognitive and emotional function for rodents and fish. The NBTA Core will provide both mechanistic and functional information.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES010356-12
Application #
8450248
Study Section
Special Emphasis Panel (ZES1-SET-V)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
12
Fiscal Year
2013
Total Cost
$301,972
Indirect Cost
$135,502
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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