Superfund Research Program
Neural and Behavioral Toxicity Assessment Core
Project Leader: Edward D. Levin
Co-Investigator: Theodore A. Slotkin (Duke University Medical Center)
Grant Number: P42ES010356
Funding Period: 2011-2022
Project Summary (2011-2017)
The Neural and Behavioral Toxicity Assessment Core provides information concerning the cellular and neurobehavioral consequences of toxicant exposures being studied in the Superfund Center. Neurotoxicant actions are evaluated by cell-based screening using neuronotypic PC12 cells, primary neurons from fetal rat cerebral cortex, and neuronal-glial co-cultures, to screen for developmental neurotoxicity across the entire spectrum of neurodevelopmental events, from cell replication to differentiation into specific neuronal phenotypes. This provides 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 provides detailed assessment of cognitive, emotional and appetitive functions affected by developmental toxicant exposures in test batteries that the researchers have designed for the diverse models studied within the Center. These neurobehavioral batteries are tailored to the rodent and fish model systems used in the Center. These complementary models are used to help the project researchers determine how the toxicant-induced molecular events, neurochemical disruption and neurocircuit miswiring cause persistent functional behavioral impairment. These 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 Neural and Behavioral Toxicity Assessment 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.