Dataset Information

Effects of embryonic exposure to polychlorinated biphenyls (PCBs) on anxiety-related behaviors in larval zebrafish.

ABSTRACT: The zebrafish (Danio rerio) is an excellent model system for assessing the effects of toxicant exposure on behavior and neurodevelopment. In the present study, we examined the effects of sub-chronic embryonic exposure to polychlorinated biphenyls (PCBs), a ubiquitous anthropogenic pollutant, on anxiety-related behaviors. We found that exposure to the PCB mixture, Aroclor (A) 1254, from 2 to 26h post-fertilization (hpf) induced two statistically significant behavioral defects in larvae at 7 days post-fertilization (dpf). First, during 135min of free swimming, larvae that had been exposed to 2ppm, 5ppm or 10ppm A1254 exhibited enhanced thigmotaxis (edge preference) relative to control larvae. Second, during the immediately ensuing 15-min visual startle assay, the 5ppm and 10ppm PCB-exposed larvae reacted differently to a visual threat, a red 'bouncing' disk, relative to control larvae. These results are consistent with the anxiogenic and attention-disrupting effects of PCB exposure documented in children, monkeys and rodents and merit further investigation.

SUBMITTER: Gonzalez ST

PROVIDER: S-EPMC4808333 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Effects of embryonic exposure to polychlorinated biphenyls (PCBs) on anxiety-related behaviors in larval zebrafish.

Gonzalez Sarah T ST Remick Dylan D Creton Robbert R Colwill Ruth M RM

Neurotoxicology 20151231

The zebrafish (Danio rerio) is an excellent model system for assessing the effects of toxicant exposure on behavior and neurodevelopment. In the present study, we examined the effects of sub-chronic embryonic exposure to polychlorinated biphenyls (PCBs), a ubiquitous anthropogenic pollutant, on anxiety-related behaviors. We found that exposure to the PCB mixture, Aroclor (A) 1254, from 2 to 26h post-fertilization (hpf) induced two statistically significant behavioral defects in larvae at 7 days ...[more]

PMID: 26748073

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Project description:BackgroundEpidemiologic studies of postnatal PCB exposure and behavior have not reported consistent evidence of adverse associations, possibly because of challenges in exposure estimation. We previously developed a pharmacokinetic model to improve estimation of children's PCB exposure.ObjectivesWe aimed to assess whether estimated serum PCB levels in infancy are associated with attention deficit/hyperactivity disorder (ADHD)-related behaviors at 8 years of age among children whose cord serum PCB levels were previously shown to be associated with ADHD-related behaviors.MethodsWe used a pharmacokinetic model to estimate monthly serum polychlorinated biphenyl (PCB)-153 levels in 441 infants (ages 1-12 months) based on parameters such as breastfeeding and cord serum PCB-153 levels. Behavior was evaluated at age 8 using the Conners' Rating Scale for Teachers (CRS-T). Associations between PCB-153 levels and ADHD-related CRS-T indices were assessed using multivariable quantile regression at the 50th and 75th percentiles of CRS-T scores, where higher percentiles reflect more adverse behaviors.ResultsCord serum PCB-153 levels (median, 38 ng/g lipids) were associated with ADHD-related behaviors, although statistical significance was observed with quantile regression models only at the 75th percentile. Associations with postnatal exposure estimates were attenuated. For example, hyperactive-impulsive behavior scores at age 8 years were 0.9 points (95% CI: 0.2, 2.5), 0.5 points (95% CI: 0.3, 2.3), and 0.3 points (95% CI: -0.2, 1.5) higher in association with interquartile range increases in serum PCB-153 at birth, 2 months, and 12 months of age, respectively.ConclusionsAssociations between estimated postnatal PCB-153 exposures and ADHD-related behaviors at 8 years of age were weaker than associations with PCB-153 concentrations measured in cord serum at birth.CitationVerner MA, Hart JE, Sagiv SK, Bellinger DC, Altshul LM, Korrick SA. 2015. Measured prenatal and estimated postnatal levels of polychlorinated biphenyls (PCBs) and ADHD-related behaviors in 8-year-old children. Environ Health Perspect 123:888-894; http://dx.doi.org/10.1289/ehp.1408084.

Project description:The gut microbiota is important for maintaining homeostasis of the host. Gut microbes represent the initial site for toxicant processing following dietary exposures to environmental contaminants. The diet is the primary route of exposure to polychlorinated biphenyls (PCBs), which are absorbed via the gut, and subsequently interfere with neurodevelopment and behavior. Developmental exposures to PCBs have been linked to increased risk of neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD), which are also associated with a high prevalence of gastrointestinal (GI) distress and intestinal dysbiosis. We hypothesized that developmental PCB exposure impacts colonization of the gut microbiota, resulting in GI pathophysiology, in a genetically susceptible host. Mouse dams expressing two heritable human mutations (double mutants [DM]) that result in abnormal Ca2+ dynamics and produce behavioral deficits (gain of function mutation in the ryanodine receptor 1 [T4826I-RYR1] and a human CGG repeat expansion [170-200 CGG repeats] in the fragile X mental retardation gene 1 [FMR1 premutation]). DM and congenic wild type (WT) controls were exposed to PCBs (0-6?mg/kg/d) in the diet starting 2 weeks before gestation and continuing through postnatal day 21 (P21). Intestinal physiology (Ussing chambers), inflammation (qPCR) and gut microbiome (16S sequencing) studies were performed in offspring mice (P28-P30). Developmental exposure to PCBs in the maternal diet caused significant mucosal barrier defects in ileum and colon (increased secretory state and tight junction permeability) of juvenile DM mice. Furthermore, PCB exposure increased the intestinal inflammatory profile (Il6, Il1?, and Il22), and resulted in dysbiosis of the gut microbiota, including altered ?-diversity, in juvenile DM mice developmentally exposed to 1?mg/kg/d PCBs when compared to WT controls. Collectively, these findings demonstrate a novel interaction between PCB exposure and the gut microbiota in a genetically susceptible host that provide novel insight into environmental risk factors for neurodevelopmental disorders.

Dataset Information

Effects of embryonic exposure to polychlorinated biphenyls (PCBs) on anxiety-related behaviors in larval zebrafish.

Publications

Effects of embryonic exposure to polychlorinated biphenyls (PCBs) on anxiety-related behaviors in larval zebrafish.

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