Levin Edward D, Chrysanthis Elizabeth, Yacisin Kari, Linney Elwood
Department of Psychiatry and Behavioral Sciences, Box #3412, Duke University Medical Center, Durham, NC 27710, USA.
Neurotoxicol Teratol. 2003 Jan-Feb;25(1):51-7. doi: 10.1016/s0892-0362(02)00322-7.
Chlorpyrifos (CPF) is a widely used insecticide, which has been shown to interfere with neurobehavioral development. Rat models have been key in demonstrating that prenatal CPF exposure causes choice accuracy deficits and motor alterations, which persist into adulthood. Complementary nonmammalian models can be useful in determining the molecular mechanisms underlying the persisting behavioral effects of developmental CPF exposure. Zebrafish with their clear chorion and extensive developmental information base provide an excellent model for assessment of molecular processes of toxicant impacted neurodevelopment. To facilitate the use of the zebrafish model and to compare it to the more typical rodent models, the behavioral phenotype of CPF toxicity in zebrafish must be well characterized. Our laboratory has developed methods for assessing spatial discrimination learning in zebrafish, which can differentiate response latency from choice accuracy in a three chambered fish tank. Low and high doses of CPF (10 and 100 ng/ml on days 1-5 postfertilization) both had significant persisting effects on both spatial discrimination and response latency over 18 weeks of testing. The high, but not the low dose, significantly accelerated mortality rates of the fish during the study from 20-38 weeks of age. Developmental exposure to either 10 or 100 ng/ml of CPF caused significant spatial discrimination impairments in zebrafish when they were adults. The impairment caused by 10 ng/ml was seen during early but not later testing, while the impairment caused by 100 ng/ml became more pronounced with continued testing. The higher dose caused a more pervasive impairment. The 10 and 100 ng/ml doses had opposite effects on response latency. The low 10 ng/ml dose significantly slowed response latency, while the high 100 ng/ml dose significant increased response latency. Both of these effects diminished with continued testing. CPF exposure during early development caused clear behavioral impairments, which lasted throughout adulthood in zebrafish. The molecular mechanisms by which early developmental CPF exposure produces these behavioral impairments expressed in adulthood can now be studied in the zebrafish model.
毒死蜱（CPF）是一种广泛使用的杀虫剂，已被证明会干扰神经行为发育。大鼠模型对于证明产前接触CPF会导致选择准确性缺陷和运动改变至关重要，这些影响会持续到成年期。互补的非哺乳动物模型有助于确定发育性CPF暴露持续行为影响的分子机制。斑马鱼具有透明的卵膜和丰富的发育信息库，为评估有毒物质影响神经发育的分子过程提供了一个极好的模型。为了便于使用斑马鱼模型并将其与更典型的啮齿动物模型进行比较，必须充分表征斑马鱼中CPF毒性的行为表型。我们实验室已经开发出评估斑马鱼空间辨别学习的方法，该方法可以在三室鱼缸中区分反应潜伏期和选择准确性。低剂量和高剂量的CPF（受精后第1 - 5天分别为10和100 ng/ml）在18周的测试中对空间辨别和反应潜伏期均有显著的持续影响。在20 - 38周龄的研究期间，高剂量（而非低剂量）显著加速了鱼类的死亡率。发育过程中接触10或100 ng/ml的CPF会使成年斑马鱼出现显著的空间辨别障碍。10 ng/ml造成的障碍在早期测试中出现，但后期未出现，而100 ng/ml造成的障碍随着持续测试变得更加明显。较高剂量导致更普遍的障碍。10和100 ng/ml剂量对反应潜伏期有相反的影响。低剂量10 ng/ml显著延长反应潜伏期，而高剂量100 ng/ml显著缩短反应潜伏期。随着持续测试，这两种影响都减弱了。早期发育期间接触CPF会导致明显的行为障碍，这种障碍在斑马鱼成年后会持续存在。现在可以在斑马鱼模型中研究早期发育性CPF暴露产生成年期表现出的这些行为障碍的分子机制。
