Experimental Medicine Program, University of British Columbia, Vancouver, Canada.
Graduate Program in Neuroscience, University of British Columbia, Vancouver, Canada.
Sci Rep. 2018 Mar 20;8(1):4890. doi: 10.1038/s41598-018-23018-w.
Zebrafish have been used to investigate motor neuron degeneration, including as a model system to examine the pathogenesis of amyotrophic lateral sclerosis (ALS). The use of zebrafish for this purpose has some advantages over other in vivo model systems. In the current paper, we show that bisphenol A (BPA) exposure in zebrafish embryos results in motor neuron degeneration with affected motor function, reduced motor axon length and branching, reduced neuromuscular junction integrity, motor neuron cell death and the presence of activated microglia. In zebrafish, motor axon length is the conventional method for estimating motor neuron degeneration, yet this measurement has not been confirmed as a valid surrogate marker. We also show that reduced motor axon length as measured from the sagittal plane is correlated with increased motor neuron cell death. Our preliminary timeline studies suggest that axonopathy precedes motor cell death. This outcome may have implications for early phase treatments of motor neuron degeneration.
斑马鱼已被用于研究运动神经元变性，包括作为研究肌萎缩侧索硬化症 (ALS) 发病机制的模型系统。与其他体内模型系统相比，斑马鱼在这方面具有一些优势。在当前的论文中，我们表明，双酚 A (BPA) 暴露在斑马鱼胚胎中会导致运动神经元变性，表现为运动功能受损、运动轴突长度和分支减少、运动神经元与肌肉连接处完整性受损、运动神经元细胞死亡和激活的小胶质细胞存在。在斑马鱼中，运动轴突长度是评估运动神经元变性的常用方法，但尚未证实该测量方法是有效的替代标志物。我们还表明，从矢状面测量的运动轴突长度与运动神经元细胞死亡增加相关。我们的初步时间线研究表明，轴突病先于运动神经元细胞死亡。这一结果可能对运动神经元变性的早期阶段治疗有意义。
