Truong Lisa, Mandrell David, Mandrell Rick, Simonich Michael, Tanguay Robert L
Department of Environmental and Molecular Toxicology, the Sinnhuber Aquatic Research Laboratory and the Environmental Health Sciences Center at Oregon State University, Corvallis, OR, United States.
Davrick Solutions, LLC, Lake Oswego, OR, United States.
Neurotoxicology. 2014 Jul;43:134-142. doi: 10.1016/j.neuro.2014.03.005. Epub 2014 Mar 24.
A substantial body of evidence has correlated the human body burdens of some polybrominated diphenyl ether (PBDE) flame retardants with cognitive and other behavioral deficits. Adult zebrafish exhibit testable learning and memory, making them an increasingly attractive model for neurotoxicology. Our goal was to develop a rapid throughput means of identifying the cognitive impact of developmental exposure to flame retardants in the zebrafish model. We exposed embryos from 6h post fertilization to 5 days post fertilization to either PBDE 47 (0.1μM), PBDE 99 (0.1μM) or PBDE 153 (0.1μM), vehicle (0.1% DMSO), or embryo medium (EM). The larvae were grown to adulthood and evaluated for the rate at which they learned an active-avoidance response in an automated shuttle box array. Zebrafish developmentally exposed to PBDE 47 learned the active avoidance paradigm significantly faster than the 0.1% DMSO control fish (P<0.0001), but exhibited significantly poorer performance when retested suggestive of impaired memory retention or altered neuromotor activity. Learning in the PBDE 153 group was not significantly different from the DMSO group. Developmental exposure to 0.1% DMSO impaired adult active avoidance learning relative to the sham group (n=39; P<0.0001). PBDE 99 prevented the DMSO effect, yielding a learning rate not significantly different from the sham group (n=36; P>0.9). Our results underscore the importance of vehicle choice in accurately assessing chemical effects on behavior. Active avoidance response in zebrafish is an effective model of learning that, combined with automated shuttle box testing, will provide a highly efficient platform for evaluating persistent neurotoxic hazard from many chemicals.
大量证据表明，人体中某些多溴二苯醚（PBDE）阻燃剂的负荷与认知及其他行为缺陷相关。成年斑马鱼具有可测试的学习和记忆能力，这使其成为神经毒理学中越来越有吸引力的模型。我们的目标是开发一种高通量方法，以确定斑马鱼模型中发育暴露于阻燃剂对认知的影响。我们将受精后6小时至受精后5天的胚胎暴露于PBDE 47（0.1μM）、PBDE 99（0.1μM）或PBDE 153（0.1μM）、溶剂（0.1%二甲基亚砜）或胚胎培养基（EM）中。幼虫成长至成年，并在自动穿梭箱阵列中评估它们学习主动回避反应的速率。在发育过程中暴露于PBDE 47的斑马鱼学习主动回避范式明显比0.1%二甲基亚砜对照组的鱼快（P<0.0001），但在重新测试时表现明显较差，提示记忆保持受损或神经运动活动改变。PBDE 153组的学习情况与二甲基亚砜组无显著差异。与假手术组相比，发育暴露于0.1%二甲基亚砜会损害成年鱼的主动回避学习（n=39；P<0.0001）。PBDE 99可防止二甲基亚砜的影响，其学习速率与假手术组无显著差异（n=36；P>0.9）。我们的结果强调了在准确评估化学物质对行为的影响时选择溶剂的重要性。斑马鱼的主动回避反应是一种有效的学习模型，结合自动穿梭箱测试，将为评估多种化学物质的持久性神经毒性危害提供一个高效的平台。
