p75NTR and sortilin increase after facial nerve injury.
OBJECTIVE
After axotomy, Schwann cells (SCs), required for successful nerve regeneration, undergo a number of cellular changes including dedifferentiation, proliferation, expression of molecules that support axon growth, and apoptosis. This study investigated the role of p75, sortilin, and proneurotrophins in SC survival after facial nerve (FN) axotomy.


METHODS
Preliminary animal study.


METHODS
With use of FN SCs, expression of p75 and its coreceptor sortilin were quantified by immunofluorescence on days 12, 22, and 52 after axotomy in vivo and by Western blot in vitro. Contralateral FNs served as a control. SC apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). To verify a causative role for p75 in FN SC death, cultured FN SCs were treated with pro-nerve growth factor (NGF), and apoptosis was determined by TUNEL.


RESULTS
Expression of p75 and sortilin increased in FN SCs distal (P < .05) to the axotomy compared with the contralateral controls for all time points. SC apoptosis also significantly increased in the distal segment compared with the contralateral and proximal portions (P < .05). ProNGF, a p75 ligand, increased apoptosis and p75 expression in primary FN SC cultures.


CONCLUSIONS
FN axotomy increases p75 and sortilin expression in SCs, which correlates with increased apoptosis. These findings suggest roles for p75 and sortilin in SC loss after FN injury. Sortilin is a novel target in promoting FN healing after injury.
Provenzano
Matthew J
MJ
Department of Otolaryngology-Head and Neck Surgery, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, U.S.A.
Xu
Ningyong
N
Ver Meer
Mark R
MR
Clark
J Jason
JJ
Hansen
Marlan R
MR
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001369:Axons / Q000187:drug effects / Q000473:pathology; D019771:Axotomy; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D020220:Facial Nerve Injuries / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D009410:Nerve Degeneration / Q000473:pathology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology*; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000502:physiology*; D012583:Schwann Cells / Q000187:drug effects / Q000473:pathology*; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D000099183:Sortilin; C514218:pro-nerve growth factor, rat; C068313:Ngfr protein, rat