Schwann cell apoptosis in the postnatal axotomized sciatic nerve is mediated via NGF through the low-affinity neurotrophin receptor

Schwann cell death is a developmentally regulated phenomenon and is also induced after peripheral nerve axotomy in neonatal rodents. In this study, we explored whether ligand-induced activation of the low-affinity neurotrophin receptor (p75^NTR) is responsible for inducing Schwann cell death in vivo. Administration of exogenous nerve growth factor (NGF) to the axotomized nerve site in wild-type animals resulted in a 2.6-fold increase in Schwann cell apoptosis in the distal nerve stumps compared to axotomy alone. No increase in apoptosis, above baseline levels, was seen in p75^NTR-mutant mice either with or without NGF. When anti-NGF antibodies were administered to the site of the peripheral nerve lesion in wild-type mice there was a reduction in the percentage of Schwann cell apoptosis to levels seen in both the quiescent state and in the axotomized nerves of the p75^NTR-mutant mice. These results demonstrate that apoptosis of Schwann cells in axotomized peripheral nerve is mediated predominantly through p75^NTR signaling and initiated via endogenously produced NGF.