Terminal Schwann Cells Are Essential for Neuromuscular Junction Function and Recovery after Nerve Injury

Abstract

Background: Terminal Schwann cells (tSCs), nonmyelinating glial cells at the neuromuscular junction (NMJ), are integral to NMJ development, function, remodeling, and response to injury. It is essential to understand their requirement for NMJ function. In this study, the authors assessed consequences of immune-mediated tSC ablation in adult S100-GFP mice of both sexes in homeostasis and after nerve injury. Methods: The authors examined NMJ morphology and function in the extensor digitorum longus muscle during homeostasis at post–tSC ablation days 3, 14, and 42 and after peroneal nerve transection and immediate repair at 3 and 6 weeks after nerve injury and tSC ablation (postinjury and ablation). Results: tSC ablation resulted in significant decreases (P < 0.05) in tSC numbers per NMJ and end plate fragmentation. NMJ innervation and EDL tetanic force were significantly decreased at post–tSC ablation day 14 (P < 0.05) and tSCs reestablished their NMJ coverage at post–tSC ablation day 42. After nerve injury, motor end plate fragmentation increased (P < 0.01) with tSC ablation compared with injured control mice. NMJ reinnervation and extensor digitorum longus tetanic force were significantly reduced (P < 0.001), even at 6 weeks postinjury and ablation, compared with control mice. Conclusion: These results add to the understanding that tSCs, with their proregenerative potential, help maintain NMJ integrity in homeostasis and are necessary for NMJ reinnervation after peripheral nerve injury. Clinical Relevance Statement: Terminal Schwann cells are integral for efficient NMJ recovery after nerve injury. This cell population may provide a novel therapeutic target to improve outcomes for patients with nerve injuries; additional investigation is warranted.