Department of Psychology, and Sheffield Institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom.
Centre for Neuroscience, University of Alberta Edmonton, T6G 2S2, Canada.
Neurobiol Dis. 2018 May;113:33-44. doi: 10.1016/j.nbd.2018.01.019. Epub 2018 Jan 31.
Selective survival of small motor nerve fibers and their neuromuscular contacts in the SOD1 transgenic mouse model of amyotrophic lateral sclerosis (ALS) suggests that smaller regenerated nerve fibers are more able to sustain reformed nerve-muscle connections as functionally intact motor units (MUs). The sciatic nerve was crushed unilaterally in SOD1 transgenic mice at 40 days of age and contractile forces of reinnervated muscles and their MUs were recorded at 90 days in order to determine the capacities of the nerves to regenerate and to form and retain functional neuromuscular connections. Reduced MU numbers in fast-twitch tibialis anterior, extensor digitorum longus and medial gastrocnemius muscles and the lesser reductions in slow-twitch soleus muscle of SOD1 transgenic mice were reversed in reinnervated muscles: there were more reinnervated MUs and their contractile forces and the muscle forces and weights increased. In line with the contrasting ability of only small not large nerve fibers to sprout to form enlarged MUs in the SOD1 transgenic mouse, the smaller regenerating nerve fibers formed enlarged MUs that were better able to survive. Because nerve fibers with and without muscle contacts were severed by the sciatic nerve crush injury, the conditioning lesion is untenable as the explanation for improved maintenance of reinnervated neuromuscular junctions. Elevated neurotrophic factor expression in axotomized motoneurons and/or denervated Schwann cells and the synapse withdrawal from axotomized motoneurons are other factors that, in addition to reduced size of nerve fibers reinnervating muscles, may account for increased survival and size of reinnervated MUs in ALS.
在肌萎缩侧索硬化症（ALS）的 SOD1 转基因小鼠模型中，小运动神经纤维及其运动终板的选择性存活表明，较小的再生神经纤维更能够维持功能完整的运动单位（MU）的重新形成的神经肌肉连接。在 SOD1 转基因小鼠 40 天时，单侧挤压坐骨神经，并在 90 天时记录再支配肌肉及其 MU 的收缩力，以确定神经的再生能力以及形成和保留功能性神经肌肉连接的能力。快速抽搐的胫骨前肌、伸趾长肌和内侧比目鱼肌中的 MU 数量减少，而 SOD1 转基因小鼠的慢抽搐比目鱼肌中的 MU 数量减少较少，在再支配的肌肉中，MU 数量增加，其收缩力、肌肉力量和重量也增加。与 SOD1 转基因小鼠中仅有小神经纤维而不是大神经纤维能够发芽形成增大的 MU 的能力形成对比，较小的再生神经纤维形成了更大的 MU，这些 MU 更能存活。由于坐骨神经挤压损伤切断了有和没有肌肉接触的神经纤维，因此条件性损伤不能作为改善再支配的神经肌肉接头维持的解释。轴突切断的运动神经元和/或去神经的施万细胞中神经营养因子表达的升高，以及轴突切断的运动神经元中的突触退缩，除了再支配肌肉的神经纤维体积减小之外，还可能是 ALS 中增加再支配 MU 的存活和大小的其他因素。
