%0 Journal Article %J Toxicology %D 2012 %T Neurodevelopmental low-dose bisphenol A exposure leads to early life-stage hyperactivity and learning deficits in adult zebrafish. %A Saili, Katerine S %A Corvi, Margaret M %A Weber, Daniel N %A Patel, Ami U %A Das, Siba R %A Przybyla, Jennifer %A Kim A Anderson %A Robyn L Tanguay %K Animals %K Behavior, Animal %K Benzhydryl Compounds %K Chromatography, High Pressure Liquid %K Dose-Response Relationship, Drug %K Embryo, Nonmammalian %K Endocrine Disruptors %K Environmental Pollutants %K Estradiol %K Hydrazines %K Hyperkinesis %K Larva %K Learning Disorders %K Maze Learning %K Phenols %K Receptors, Estrogen %K Receptors, G-Protein-Coupled %K Reversal Learning %K Teratogens %K Zebrafish %X

Developmental bisphenol A (BPA) exposure has been implicated in adverse behavior and learning deficits. The mode of action underlying these effects is unclear. The objectives of this study were to identify whether low-dose, developmental BPA exposure affects larval zebrafish locomotor behavior and whether learning deficits occur in adults exposed during development. Two control compounds, 17β-estradiol (an estrogen receptor ligand) and GSK4716 (a synthetic estrogen-related receptor gamma ligand), were included. Larval toxicity assays were used to determine appropriate BPA, 17β-estradiol, and GSK4716 concentrations for behavior testing. BPA tissue uptake was analyzed using HPLC and lower doses were extrapolated using a linear regression analysis. Larval behavior tests were conducted using a ViewPoint Zebrabox. Adult learning tests were conducted using a custom-built T-maze. BPA exposure to <30μM was non-teratogenic. Neurodevelopmental BPA exposure to 0.01, 0.1, or 1μM led to larval hyperactivity or learning deficits in adult zebrafish. Exposure to 0.1μM 17β-estradiol or GSK4716 also led to larval hyperactivity. This study demonstrates the efficacy of using the zebrafish model for studying the neurobehavioral effects of low-dose developmental BPA exposure.

%B Toxicology %V 291 %P 83-92 %8 01/2012 %G eng %N 1-3 %1 http://www.ncbi.nlm.nih.gov/pubmed/22108044?dopt=Abstract %R 10.1016/j.tox.2011.11.001 %0 Journal Article %J Environ Health Perspect %D 2009 %T Developmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats. %A Yang, Dongren %A Kim, Kyung Ho %A Phimister, Andrew %A Bachstetter, Adam D %A Ward, Thomas R %A Stackman, Robert W %A Mervis, Ronald F %A Wisniewski, Amy B %A Klein, Sabra L %A Kodavanti, Prasada Rao S %A Kim A Anderson %A Wayman, Gary %A Pessah, Isaac N %A Lein, Pamela J %K Animals %K Animals, Newborn %K Body Weight %K Chlorodiphenyl (54% Chlorine) %K Dendrites %K Female %K Gene Expression Regulation, Developmental %K Green Fluorescent Proteins %K Litter Size %K Maze Learning %K Memory %K Microtubule-Associated Proteins %K Neuronal Plasticity %K Pregnancy %K Prenatal Exposure Delayed Effects %K Rats %K Rats, Sprague-Dawley %K Ryanodine Receptor Calcium Release Channel %K Sex Ratio %X

BACKGROUND: Neurodevelopmental disorders are associated with altered patterns of neuronal connectivity. A critical determinant of neuronal connectivity is the dendritic morphology of individual neurons, which is shaped by experience. The identification of environmental exposures that interfere with dendritic growth and plasticity may, therefore, provide insight into environmental risk factors for neurodevelopmental disorders.

OBJECTIVE: We tested the hypothesis that polychlorinated biphenyls (PCBs) alter dendritic growth and/or plasticity by promoting the activity of ryanodine receptors (RyRs).

METHODS AND RESULTS: The Morris water maze was used to induce experience-dependent neural plasticity in weanling rats exposed to either vehicle or Aroclor 1254 (A1254) in the maternal diet throughout gestation and lactation. Developmental A1254 exposure promoted dendritic growth in cerebellar Purkinje cells and neocortical pyramidal neurons among untrained animals but attenuated or reversed experience-dependent dendritic growth among maze-trained littermates. These structural changes coincided with subtle deficits in spatial learning and memory, increased [3H]-ryanodine binding sites and RyR expression in the cerebellum of untrained animals, and inhibition of training-induced RyR upregulation. A congener with potent RyR activity, PCB95, but not a congener with negligible RyR activity, PCB66, promoted dendritic growth in primary cortical neuron cultures and this effect was blocked by pharmacologic antagonism of RyR activity.

CONCLUSIONS: Developmental exposure to PCBs interferes with normal patterns of dendritic growth and plasticity, and these effects may be linked to changes in RyR expression and function. These findings identify PCBs as candidate environmental risk factors for neurodevelopmental disorders, especially in children with heritable deficits in calcium signaling.

%B Environ Health Perspect %V 117 %P 426-35 %8 03/2009 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/19337518?dopt=Abstract %R 10.1289/ehp.11771