Ablation of Terminal Schwann Cells after Nerve Injury
Katherine Bernadette Santosa, M.D.; Washington University, Saint Louis, MO; Albina Jablonka-Shariff, Ph.D.; Division of Plastic and Reconstructive Surgery, Washington University, Saint Louis, MO; Alison K. Snyder-Warwick, MD; Plastic Surgery, Washington University School of Medicine, St. Louis, MO
Purpose: Terminal Schwann cells (tSCs) are a special type of supportive glial cells that reside at the neuromuscular junction (NMJ), and are particularly active during reinnervation. After nerve injury, tSCs induce nerve terminal sprouting and extend elaborate processes beyond the NMJ, which help guide regenerating axons. While tSCs are known to support NMJ reinnervation, the requirement of tSCs for and specific contributions to NMJ reinnervation in mammalian species is not known. By ablating tSCs in mice, we sought to determine the role of tSCs on the health of the NMJ after nerve injury.
Methods: Adult S100-GFP mice underwent right sciatic nerve transection with repair (t=0). Twenty-four hours later, these mice underwent injection of their right extensor digitorum longus (EDL) muscles with either GD3 anti-disialosyl antibodies to ablate tSCs (i.e. experimental group) or an equivalent volume of Lactated Ringerís (i.e. control group). At t=1 or 6 weeks after the initial nerve injury, animals were sacrificed, and EDL muscles were harvested. We then evaluated NMJ morphology within the EDL utilizing confocal microscopy.
Results: Following tSC ablation with GD3 anti-disialosyl antibodies, the total number of tSCs per NMJ was reduced at 6 weeks following nerve injury compared to controls (3 vs. 2, p<0.0001). In addition to being fewer in number, tSCs present at 6 weeks after injury and tSC ablation exhibited weaker S100 staining intensity than in controls. Endplate fragmentation was notably greater in mice that underwent tSC ablation versus those that received sham injections (52.2% vs. 13.2%).
Conclusions: Our data suggest that we were successfully able to specifically target tSCs in mice using the GD3 anti-disialosyl antibody. Moreover, tSC ablation 24 hours after nerve injury leads to increased fragmentation of endplates, suggesting an important role of tSCs in the health and maintenance of the NMJ following nerve injury and repair. Further investigation is ongoing to determine the importance of tSCs on reinnervation of the NMJ following nerve injury.
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