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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Final Progress Reports: Duke University: Developmental Neurotoxicants: Sensitization, Consequences, and Mechanisms

Superfund Research Program

Developmental Neurotoxicants: Sensitization, Consequences, and Mechanisms

Project Leader: Theodore A. Slotkin (Duke University Medical Center)
Grant Number: P42ES010356
Funding Period: 2011-2017
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Final Progress Reports

Year:   2016 

This project studies how exposures to toxicants from different chemical classes converge on common neurodevelopmental events, producing similar adverse outcomes and potentially, additive or synergistic interactions that produce a population with enhanced vulnerability. In the past year, the research team focused on development of an in vitro model to characterize this convergence, using neural stem cells derived from the developing brain. Cells were selected at the time when the formation of neurons and glial support cells are determined, then their response to a wide variety of neurotoxicants was evaluated. Three broad classifications of effect based on the expression of either the neural or glial cell phenotypes were found. Glucocorticoids (a class of steroids), organophosphate pesticides, nickel, and nicotine suppressed expression of the glial phenotype while having little or no effect on the neuronal phenotype. Organochlorine pesticides acting on GABAA receptors promoted the glial phenotype and suppressed the neuronal phenotype. Tobacco smoke extract and silver elicited cytotoxicity, with major cell loss and suppression of cell differentiation into both phenotypes. Researchers then went on to use this test system to show that complex environmental mixtures of polycyclic aromatic hydrocarbons (PAHs, a by-product of combustion and many industrial processes) have distinctly different neurodevelopmental effects from equivalent concentrations of single PAHs, indicating the potential for much worse outcomes from such exposures to environmental mixtures. These findings point to new screening tools to test for developmental neurotoxicity across widely different compounds, discriminating among the pathways that actually determine developmental neurotoxicity, rather than relying on chemical similarity.

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