p75NTR and Sortilin Increase After Facial Nerve Injury

Objectives: After axotomy, Schwann cells (SCs), required for successful nerve regeneration, undergo a number of cellular changes including dedifferentiation, proliferation, expression of molecules that support axon growth, and apoptosis. This study investigated the role of p75(NTR), sortilin, and proneurotrophins in SC survival after facial nerve (FN) axotomy. Study Design: Preliminary animal study. Methods: With use of FN SCs, expression of p75(NTR) and its coreceptor sortilin were quantified by immunofluorescence on days 12, 22, and 52 after axotomy in vivo and by Western blot in vitro. Contralateral FNs served as a control. SC apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). To verify a causative role for p75(NTR) in FN SC death, cultured FN SCs were treated with pro-nerve growth factor (NGF), and apoptosis was determined by TUNEL. Results: Expression of p75(NTR) and sortilin increased in FN SCs distal (P < .05) to the axotomy compared with the contralateral controls for all time points. SC apoptosis also significantly increased in the distal segment compared with the contralateral and proximal portions (P < .05). ProNGF, a p75(NTR) ligand, increased apoptosis and p75(NTR) expression in primary FN SC cultures. Conclusion: FN axotomy increases p75(NTR) and sortilin expression in SCs, which correlates with increased apoptosis. These findings suggest roles for p75(NTR) and sortilin in SC loss after FN injury. Sortilin is a novel target in promoting FN healing after injury.