Department of Kinesiology, St. Ambrose University, Davenport, IA 52803, USA.
LBEPS, Univ Evry, IRBA, Université Paris Saclay, 91025 Evry, France.
Int J Mol Sci. 2021 Dec 24;23(1):169. doi: 10.3390/ijms23010169.
Denervation of skeletal muscle is a debilitating consequence of injury of the peripheral nervous system, causing skeletal muscle to experience robust atrophy. However, the molecular mechanisms controlling the wasting of skeletal muscle due to denervation are not well understood. Here, we demonstrate that transection of the sciatic nerve in Sprague-Dawley rats induced robust skeletal muscle atrophy, with little effect on the neuromuscular junction (NMJ). Moreover, the following study indicates that all three arms of the unfolded protein response (UPR) are activated in denervated skeletal muscle. Specifically, ATF4 and ATF6 are elevated in the cytoplasm of skeletal muscle, while XBP1 is elevated in the nuclei of skeletal muscle. Moreover, XBP1 is expressed in the nuclei surrounding the NMJ. Altogether, these results endorse a potential role of the UPR and, specifically, XBP1 in the maintenance of both skeletal muscle and the NMJ following sciatic nerve transection. Further investigations into a potential therapeutic role concerning these mechanisms are needed.
神经肌肉失神经支配是周围神经系统损伤的一种使人虚弱的后果，导致骨骼肌经历显著的萎缩。然而，控制由于失神经支配导致的骨骼肌消耗的分子机制还没有被很好地理解。在这里，我们证明了在 Sprague-Dawley 大鼠中切断坐骨神经会引起显著的骨骼肌萎缩，而对神经肌肉接点（NMJ）几乎没有影响。此外，以下研究表明， unfolded protein response（UPR）的三个分支都在失神经支配的骨骼肌中被激活。具体来说，ATF4 和 ATF6 在骨骼肌的细胞质中升高，而 XBP1 在骨骼肌的核中升高。此外，XBP1 在 NMJ 周围的核中表达。总之，这些结果支持 UPR 的一个潜在作用，特别是 XBP1 在坐骨神经切断后维持骨骼肌和 NMJ 的作用。需要进一步研究这些机制的潜在治疗作用。
