Département de neurosciences, Université de Montréal, Montréal, Québec H3C 3J7, Canada
Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec H3T 1C5, Canada.
eNeuro. 2020 Feb 26;7(1). doi: 10.1523/ENEURO.0388-19.2020. Print 2020 Jan/Feb.
Progressive loss of neuromuscular junctions (NMJs) is an early event in amyotrophic lateral sclerosis (ALS), preceding the global degeneration of motor axons and being accompanied by new axonal sprouting within the same axonal arbor. Some aspects of ALS onset and progression seem to be affected by sex in animal models of the disease. However, whether there are sex-specific differences in the pattern or time course of NMJ loss and repair within single motor axons remains unknown. We performed further analysis of a previously published dataset, obtained from male and female SOD1 mice. We found that NMJ losses are as frequent in male and female motor axons but, intriguingly, axonal sprouting is more frequent in female than male mice, resulting in a net increase of axonal arborization. Interestingly, these numerous new axonal branches in female mice are associated with a slightly faster decline in grip strength, increased NMJ denervation, and reduced α-motor neuron survival. Collectively, these results suggest that excessive axonal sprouting and motor-unit (MU) expansion in female SOD1 mice are maladaptive during ALS progression.
运动神经元轴突（MNs）丧失是肌萎缩侧索硬化症（ALS）的早期事件，先于运动轴突的全向退行，并伴有同一轴突树突内的新生轴突发芽。疾病动物模型中的某些 ALS 发病和进展方面似乎受性别影响。然而，在单个运动轴突内，神经肌肉接头（NMJ）丧失和修复的模式或时间进程是否存在性别特异性差异仍不清楚。我们对先前发表的数据集进行了进一步分析，该数据集来自雄性和雌性 SOD1 小鼠。我们发现 NMJ 丧失在雄性和雌性运动轴突中同样频繁，但有趣的是，雌性小鼠的轴突发芽比雄性更为频繁，导致轴突树突的净增加。有趣的是，这些雌性小鼠中大量的新轴突分支与握力下降稍快、NMJ 去神经支配增加以及α-运动神经元存活减少有关。总的来说，这些结果表明，雌性 SOD1 小鼠在 ALS 进展过程中过度的轴突发芽和运动单位（MU）扩张是适应不良的。
