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

• Published in: Glia 2012-01, Vol.60 (4), p.639-650
• Main Authors: Morton, Paul D., Johnstone, Joshua T., Ramos, Angel Y., Liebl, Daniel J., Bunge, Mary B., Bethea, John R.
• Format: Article
• Language: English
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.22297

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 significantly enhanced at 65 days in transgenic animals. Compact re-myelination and Remak bundle organization were significantly compromised at 31 days and restored by 65 days post injury. Together, these data indicate that inhibition of NF- κB activation in SCs transiently delays axonal regeneration and compact re-myelination. Manipulating the temporal activation of nuclear factor-κB in Schwann cells may offer new therapeutic avenues for PNS and CNS regeneration.