Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA.
Neurotoxicol Teratol. 2012 Jul;34(4):458-65. doi: 10.1016/j.ntt.2012.04.010. Epub 2012 May 8.
Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders.
神经行为障碍，如焦虑、自闭症和注意缺陷多动障碍，通常受到遗传和环境因素的影响。尽管近年来已经确定了一些遗传风险因素，但对于导致神经行为障碍或导致遗传易感性个体疾病进展的环境因素知之甚少。一种引起关注的环境因素是毒死蜱，一种广泛用于农业的有机磷农药，在环境中普遍存在。在本研究中，我们使用斑马鱼幼虫研究了亚慢性毒死蜱暴露对发育过程中与焦虑相关的行为的影响。我们发现，在发育过程中，亚慢性暴露于 0.01 或 0.1 μM 的毒死蜱会导致 7 日龄斑马鱼幼虫出现特定的行为缺陷。幼虫的游泳速度和贴壁性降低，但回避行为没有变化。暴露于 0.001 μM 的毒死蜱不会影响游泳、贴壁性或回避行为，而暴露于 1 μM 的毒死蜱会引起行为缺陷，但也会引起幼虫形态缺陷。由于贴壁性，即对边缘的偏好，是斑马鱼幼虫的一种焦虑相关行为，我们提出亚慢性毒死蜱暴露会干扰焦虑相关行为的发育。这项研究的结果为研究受环境相关浓度有机磷农药影响的分子、细胞、发育和神经机制提供了一个良好的起点。更详细地了解这些机制对于开发预测模型和完善健康政策以预防有毒物质引起的神经行为障碍非常重要。
