title: Nuclear factor-κB activation in Schwann cells regulates regeneration and remyelination.
abstract: Schwann cells (SCs) are crucial for peripheral nerve development and regeneration; however, the intrinsic regulatory mechanisms governing postinjury 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 remyelination 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 remyelination. Manipulating the temporal activation of nuclear factor-κB in Schwann cells may offer new therapeutic avenues for PNS and CNS regeneration.
authors.affiliation: The Miami Project To Cure Paralysis, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Morton
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Johnstone
authors.forename: Angel Y
authors.initials: AY
authors.lastname: Ramos
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Liebl
authors.forename: Mary Bartlett
authors.initials: MB
authors.lastname: Bunge
authors.forename: John R
authors.initials: JR
authors.lastname: Bethea
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019771:Axotomy / Q000379:methods; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D020220:Facial Nerve Injuries / Q000150:complications / Q000209:etiology; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009046:Motor Neurons / Q000473:pathology; D018993:Myelin P0 Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D009416:Nerve Regeneration / Q000502:physiology*; D016900:Neurofilament Proteins / Q000378:metabolism; D011930:Reaction Time / Q000235:genetics; D020127:Recovery of Function / Q000235:genetics; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D013266:Stilbamidines; D013997:Time Factors; D014855:Wallerian Degeneration / Q000209:etiology / Q000473:pathology*
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; C560546:Mpz protein, mouse; D018993:Myelin P0 Protein; D016900:Neurofilament Proteins; C000606205:Nfkbia protein, mouse; D013266:Stilbamidines; C051774:neurofilament protein H; D000072000:NF-KappaB Inhibitor alpha