Nuclear Factor-κB Activation in Schwann Cells Regulates Regeneration and Re-Myelination

Schwann cells (SCs) are crucial for peripheral nerve development and regeneration; however, the intrinsic regulatory mechanisms governing post-injury responses are poorly understood. Activation and deacetylation of nuclear factor-κB (NF- κB) in SCs have been implicated as prerequisites for peripheral nerve myelination. Using GFAP-IκBα-dn mice, in which NF- κB transcriptional activation is inhibited in SCs, we found no discernable differences in the quantity or structure of myelinated axons in adult facial nerves. Following crush injury, axonal regeneration was impaired at 31 days and greatly improved at 65 days in GFAP-IκBα-dn mutants. Compact re-myelination and sensory fiber organization were significantly compromised at 31 days and restored by 65 days. Together, these data indicate that NF- κB activation in SCs is dispensable for peripheral nerve myelination in adults, but required for early re-myelination and axonal regeneration. SC myelination during development and following injury in adult mice may hinge on different transcriptional cascades; these findings may offer new therapeutic avenues for PNS and CNS regeneration.