Terminal Schwann cells are essential for neuromuscular junction function and recovery after nerve injury

Background– Terminal Schwann cells (tSCs), non-myelinating 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, we assessed consequences of immune-mediated tSC ablation in adult S100 -GFP mice of both sexes in homeostasis and after nerve injury. Methods– We examined NMJ morphology and function in the extensor digitorum longus (EDL) muscle during homeostasis at post-tSC ablation days (PAD) 3, 14 and 42, and after peroneal nerve transection and immediate repair at 3 and 6 weeks post-nerve injury and tSC ablation (post-injury and ablation, PIA). Results– Terminal Schwann cell ablation resulted in significant decreases (p<0.05) in tSC numbers per NMJ and endplate fragmentation. NMJ innervation and EDL tetanic force significantly decreased at PAD14 (p<0.05), and tSCs re-established their NMJ coverage at PAD42. After nerve injury, motor endplate fragmentation increased (p<0.01) with tSC ablation compared with injured control mice. NMJ reinnervation and EDL tetanic force were significantly reduced (p<0.001), even at 6 weeks PIA, compared to control mice. Conclusions– These results add to the understanding that tSCs, with their pro-regenerative potential, help maintain NMJ integrity in homeostasis and are necessary for NMJ reinnervation following 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.