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Progress Reports: Duke University: Cholinergic and Monoaminergic Mechanisms of Persistent Neurobehavioral Toxicity

Superfund Research Program

Cholinergic and Monoaminergic Mechanisms of Persistent Neurobehavioral Toxicity

Project Leader: Edward D. Levin
Co-Investigators: Theodore A. Slotkin (Duke University Medical Center), Frederic J. Seidler
Grant Number: P42ES010356
Funding Period: 2017-2022
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Progress Reports

Year:   2018  2017 

Edward D. Levin, Ph.D., and his researchers for the Cholinergic and Monoaminergic Mechanisms of Persistent Neurobehavioral Toxicity Project provided new information concerning long-term behavioral effects of gestational exposure to benzo[a]pyrene (BaP). In collaboration with NIEHS Children’s Environmental Health and Disease Prevention Center, the Project found that exposure to low, chronic BaP during gestation in rats caused persistent, sex-selective neurochemical and behavioral effects. Sex-selective effects were found in four behavioral tests, assessed through adolescence into adulthood. For example, in the novelty suppressed feeding test, both nicotine and BaP caused a significant reduction in fear response. The researchers’ neurochemical results show nicotine’s effects on the development of acetylcholine and serotonin systems is worsened by BaP coexposure. Combination of the two agents contributes to greater impact of tobacco smoke on the developing brain. These are important implications for the relative safety in pregnancy of nicotine-containing products compared to combusted tobacco, active maternal smoking and secondhand exposure, and for effects of such agents in “dirty” environments with high polycyclic aromatic hydrocarbons co-exposure. The impacts of gestational BaP exposure and the relationship between sex-selective behavioral and neurochemical effects will be determined.

In zebrafish, Levin and his researchers evaluated the effects of exposure to organophosphate flame retardants (OPFRs). Presently, little is known about developmental neurotoxicity or behavioral consequences of OPFR exposure. The researchers aimed to characterize life-long neurobehavioral effects of four widely used OPFRs. Their tests showed chemical-specific, short-term effects of altered motility in larvae, and long-term impairment of anxiety-related behavior in adults from three OPFRs. In conclusion, the research team’s findings indicate that OPFRs may not be a safe alternative to the phased-out brominated flame retardants and may cause behavioral impacts throughout the lifespan.

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