Department of Integrative Medical Biology, Section for Anatomy, Umeå University, Umeå, Sweden.
PLoS One. 2013;8(2):e57473. doi: 10.1371/journal.pone.0057473. Epub 2013 Feb 26.
The pathophysiology of amyotrophic lateral sclerosis (ALS) is very complex and still rather elusive but in recent years evidence of early involvement of the neuromuscular junctions (NMJs) has accumulated. We have recently reported that the human extraocular muscles (EOMs) are far less affected than limb muscles at the end-stage of ALS from the same donor. The present study aimed to compare the differences in synaptic protein composition at NMJ and in nerve fibers between EOM and limb muscles from ALS donors and controls. Neurofilament light subunit and synaptophysin decreased significantly at NMJs and in nerve fibers in limb muscles with ALS whereas they were maintained in ALS EOMs. S100B was significantly decreased at NMJs and in nerve fibers in both EOMs and limb muscles of ALS donors, but other markers confirmed the presence of terminal Schwann cells in these NMJs. p75 neurotrophin receptor was present in nerve fibers but absent at NMJs in ALS limb muscles. The EOMs were able to maintain the integrity of their NMJs to a very large extent until the end-stage of ALS, in contrast to the limb muscles. Changes in Ca(2+) homeostasis, reflected by altered S100B distribution, might be involved in the breakdown of nerve-muscle contact at NMJs in ALS.
肌萎缩侧索硬化症（ALS）的病理生理学非常复杂，至今仍难以捉摸，但近年来越来越多的证据表明神经肌肉接头（NMJ）的早期参与。我们最近报道，来自同一供体的 ALS 终末期，与肢体肌肉相比，人体眼外肌（EOM）受影响小得多。本研究旨在比较 ALS 供体和对照者的 EOM 和肢体肌肉 NMJ 和神经纤维中突触蛋白组成的差异。神经丝轻链和突触素在 ALS 肢体肌肉的 NMJ 和神经纤维中显著减少，而在 ALS EOM 中则保持不变。S100B 在 ALS 供体的 EOM 和肢体肌肉的 NMJ 和神经纤维中均显著减少，但其他标志物证实这些 NMJ 中存在终末施万细胞。p75 神经营养因子受体存在于神经纤维中，但在 ALS 肢体肌肉的 NMJ 中缺失。EOM 能够在很大程度上保持其 NMJ 的完整性，直到 ALS 的终末期，这与肢体肌肉不同。Ca（2+）稳态的改变，反映在 S100B 分布的改变，可能参与了 ALS 中 NMJ 神经肌肉接触的破坏。
