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

Katerine S. Saili; Margaret M. Corvi; Daniel N. Weber; Ami U. Patel; Siba R. Das; Jennifer Przybyla; Kim A. Anderson; Robert L. Tanguay

doi:10.1016/j.tox.2011.11.001

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

Katerine S. Saili, Margaret M. Corvi, Daniel N. Weber, Ami U. Patel, Siba R. Das, Jennifer Przybyla, Kim A. Anderson, Robert L. Tanguay

Research output: Contribution to journal › Article › peer-review

146 Scopus citations

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 <30 μM was non-teratogenic. Neurodevelopmental BPA exposure to 0.01, 0.1, or 1 μM led to larval hyperactivity or learning deficits in adult zebrafish. Exposure to 0.1 μM 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.

Original language	English (US)
Pages (from-to)	83-92
Number of pages	10
Journal	Toxicology
Volume	291
Issue number	1-3
DOIs	https://doi.org/10.1016/j.tox.2011.11.001
State	Published - Jan 27 2012
Externally published	Yes

Bibliographical note

Funding Information:
The authors thank C. Buchner, C. Barton, B. McCauslin, J. Dobson, and E. Johnson for fish husbandry and maintenance at the Sinnhuber Aquatic Research Laboratory, and H. Truong for providing the PERL script used to analyze larval behavior data. This work was supported by grants T32ES7060 (R.L.T.), P30 ES000210 (R.L.T.), and R21ES018970 (R.L.T.) from the National Institutes of Health, Research or Community Outreach and Education Grant (D.N.W.) from the NIEHS Children's Environmental Health Sciences Core , and a United States Environmental Protection Agency (EPA) Science to Achieve Results (STAR) Graduate Fellowship (K.S.S.). EPA has not officially endorsed this publication and the views expressed herein do not necessarily reflect the views of the EPA.

Keywords

Behavior
Bisphenol A
Endocrine disruptor
Hyperactivity
Learning
Zebrafish

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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 <30 μM was non-teratogenic. Neurodevelopmental BPA exposure to 0.01, 0.1, or 1 μM led to larval hyperactivity or learning deficits in adult zebrafish. Exposure to 0.1 μM 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.",

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

Abstract

Bibliographical note

Keywords

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