全反式维甲酸暴露对斑马鱼的神经毒性效应

Effect of All-Trans-Retinoic Acid Exposure on Neurotoxicity of Zebrafish

探讨全反式维甲酸(atRA)暴露对斑马鱼胚胎及幼鱼神经毒性效应和机制。以不同浓度(0,5,10和20 nmol/L)的atRA暴露斑马鱼胚胎,并探讨了斑马鱼自发胎动、幼鱼运动活力、可视化mbp荧光蛋白及神经相关基因表达与atRA暴露的关系。研究结果显示,与对照组相比,10和20 nmol/L的atRA暴露可显著降低斑马鱼胚胎自发运动活力,分别下降25.6%和50.8%;atRA处理下,幼鱼对光暗转换的刺激较为敏感,幼鱼总运动距离和运动速度均出现显著下降;20 nmol/L atRA暴露使得斑马鱼大脑中mbp蛋白表达减少38.7%,大脑形态的缺陷以及脑部神经复杂程度也相应减少。此外,髓磷脂碱性蛋白mbp以及突触素蛋白syn2α mRNA表达量仅为对照组的41.2%和54.6%。以上研究结果显示:atRA对斑马鱼胚胎及幼鱼具有显著的神经毒性,并且可以通过抑制mbp与syn2α的表达干扰斑马鱼胚胎早期的神经发育及行为活力。

The neurotoxic effects and mechanism of all-trans-retinoic acid(atRA)in embryo and larval zebrafish were investigated in the present work.Embryo and larval zebrafish were exposed to different concentrations of atRA(0,5,10 and 20 nmol/L)to explore the effects of atRA on the embryonic spontaneous movement,larval swimming speed,visual mbp(myelin basic protein)fluorescent protein and neuro-related gene expression in zebrafish.The results showed that,compared with the control group,the spontaneous motor activity of zebrafish embryos is significantly reduced by 25.6% and 50.8% after the exposure to 10 and 20 nmol/L atRA,respectively.Meanwhile,the larval fish are more sensitive to the stimulation of light to dark switching,and the total movement distance and average movement speed of larval fish decrease significantly with atRA treatment.Furthermore,the exposure to 20 nmol/L atRA results in a decreased expression of mbp protein by 38.7% in the brain of zebrafish,defective brain morphology and decreased neurocomplexity.In addition,the mRNA expression levels of myelin basic protein mbp and synaptophysin protein syn2α are only 41.2% and 54.6% of those in the control group.These results suggest that atRA has significant neurotoxicity on zebrafish embryos and larval fish,which can interfere with the early neurodevelopment and behavioral activity of zebrafish embryos by inhibiting the expression of mbp and syn2α.