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

Neurodevelopmental low-dose bisphenol A exposure leads to early life-stage hyperactivity and learning deficits in adult zebrafish.
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DOI:
10.1016/j.tox.2011.11.001
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发表时间:
2012-01-27
期刊:
影响因子:
4.5
通讯作者:
Tanguay RL
Tanguay RL
中科院分区:
医学3区
文献类型:
--
作者:
Saili KS;Corvi MM;Weber DN;Patel AU;Das SR;Przybyla J;Anderson KA;Tanguay RL

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发育中的双酚A(BPA)暴露与不良行为和学习障碍有关。这些影响背后的行动模式尚不清楚。采用斑马鱼模型研究发育中双酚A(BPA)暴露对大鼠神经行为的影响。这项研究的目的是确定低剂量的发育性双酚A暴露是否影响斑马鱼幼体的运动行为,以及在发育过程中暴露的成年斑马鱼是否会出现学习障碍。包括两个对照化合物,17β-雌二醇(雌激素受体配体)和GSK4716(合成的雌激素相关受体γ配体)。用幼虫毒性试验确定了行为测试所需的双酚A、17β-雌二醇和GSK4716的适宜浓度。用高效液相色谱法分析双酚A的组织摄取,并用线性回归分析外推较低剂量。幼虫行为测试是使用视点斑马盒进行的。成人学习测试使用定制的T形迷宫进行。双酚A暴露于≤30μM对斑马鱼无致畸作用。暴露于0.010.1或1μM的神经发育双酚A可导致成年斑马鱼幼体活动过度或学习障碍。暴露于0.1μM17β-雌二醇或GSK4716也可导致幼虫过度活动。这项研究证明了使用斑马鱼幼体模型研究低剂量发育双酚A暴露对神经行为的影响的有效性。
Developmental bisphenol A (BPA) exposure has been implicated in adverse behavior and learning deficits. The mode of action underlying these effects is unclear. The zebrafish model was employed to investigate the neurobehavioral effects of developmental bisphenol A (BPA) exposure. 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 nonteratogenic in zebrafish. 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 larval zebrafish model for studying the neurobehavioral effects of low-dose developmental BPA exposure.
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