gsk-4716 and Learning-Disabilities

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.

Topics: Animals; Behavior, Animal; Benzhydryl Compounds; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Embryo, Nonmammalian; Endocrine Disruptors; Environmental Pollutants; Estradiol; Hydrazines; Hyperkinesis; Larva; Learning Disabilities; Maze Learning; Phenols; Receptors, Estrogen; Receptors, G-Protein-Coupled; Reversal Learning; Teratogens; Zebrafish