Neurodevelopmental low-dose bisphenol A exposure leads to early life-stage hyperactivity and learning deficits in adult zebrafish

Toxicology. 2012 Jan 27;291(1-3):83-92. doi: 10.1016/j.tox.2011.11.001. Epub 2011 Nov 15.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Benzhydryl Compounds
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian / metabolism
  • Endocrine Disruptors / pharmacokinetics
  • Endocrine Disruptors / toxicity*
  • Environmental Pollutants / pharmacokinetics
  • Environmental Pollutants / toxicity*
  • Estradiol / pharmacology
  • Hydrazines / pharmacology
  • Hyperkinesis / chemically induced*
  • Larva
  • Learning Disabilities / chemically induced*
  • Learning Disabilities / psychology*
  • Maze Learning / drug effects
  • Phenols / pharmacokinetics
  • Phenols / toxicity*
  • Receptors, Estrogen / drug effects
  • Receptors, G-Protein-Coupled / drug effects
  • Reversal Learning / drug effects
  • Teratogens / toxicity
  • Zebrafish / physiology*

Substances

  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Environmental Pollutants
  • GSK 4716
  • Hydrazines
  • Phenols
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • Teratogens
  • Estradiol
  • bisphenol A