title: Neurodevelopmental low-dose bisphenol A exposure leads to early life-stage hyperactivity and learning deficits in adult zebrafish.
abstract: 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.
authors: Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97333, USA.
authors: Katerine S
authors: KS
authors: Saili
authors: Margaret M
authors: MM
authors: Corvi
authors: Daniel N
authors: DN
authors: Weber
authors: Ami U
authors: AU
authors: Patel
authors: Siba R
authors: SR
authors: Das
authors: Jennifer
authors: J
authors: Przybyla
authors: Kim A
authors: KA
authors: Anderson
authors: Robert L
authors: RL
authors: Tanguay
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001559:Benzhydryl Compounds; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000378:metabolism; D052244:Endocrine Disruptors / Q000493:pharmacokinetics / Q000633:toxicity*; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D004958:Estradiol / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D006948:Hyperkinesis / Q000139:chemically induced*; D007814:Larva; D007859:Learning Disabilities / Q000139:chemically induced* / Q000523:psychology*; D018782:Maze Learning / Q000187:drug effects; D010636:Phenols / Q000493:pharmacokinetics / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects; D012193:Reversal Learning / Q000187:drug effects; D013723:Teratogens / Q000633:toxicity; D015027:Zebrafish / Q000502:physiology*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004958:Estradiol; D006834:Hydrazines; D010636:Phenols; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D013723:Teratogens; C545235:GSK 4716; C006780:bisphenol A; D000098826:Bisphenol A Compounds