TNFα mediates Schwann cell death by upregulating p75NTR expression without sustained activation of NFκB

Abstract

Administration of tumour necrosis factor α (TNFα) to axotomised mouse neonatal sciatic nerves increased Schwann cell apoptosis in the distal nerve segments, 5-fold greater than axotomy alone. TNFα upregulated the low affinity neurotrophin receptor, p75NTR, indicative of phenotype reversion in Schwann cells. Furthermore, re-expression of p75NTR and downregulation of the pro-myelinating transcription factor, Oct 6, in Schwann cells occurred by treatment with TNFα, even after the maturation of these cells with brain derived neurotrophic factor (BDNF). TNFα treatment of Schwann cells produced only a transient activation of NFκB. More importantly, in NFκB (p65) mutant mice, axotomy increased Schw..