Decreased c-Jun expression correlates with impaired spinal motoneuron regeneration in aged mice following sciatic nerve crush
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AbstractPost-injury nerve regeneration of the peripheral nervous system declines with age, but the mechanisms underlying the weakened axonal regeneration are not well understood. Increased synthesis and activity of the AP-1 transcription factor c-Jun have been implicated in efficient motor axonal regeneration. In the present study, we evaluated the hypothesis that the impaired regenerative capacity in the aged is associated with impaired induction of c-Jun. In non-manipulated young adult or aged mice, no c-Jun and its phosphorylated form were detected in the ventral horn of the spinal cord. Following nerve crush, significant c-Jun and phosphorylated c-Jun occurred in the injured motoneurons of young adult mice, but not in aged animals. In accord with the immunohistochemistry, Western blots also showed that sciatic nerve crush induced c-Jun and its phosphorylation expression in the ventral horn of young adult but not in aged mice. Changes in c-Jun mRNA level detected by in situ hybridization are congruent with that in c-Jun protein content, showing an increase at 5 days after crush in young adult but not aged. Moreover, compared with young adult mice, aged mice showed impaired motor axonal regeneration. These results demonstrate that the impaired motor axonal regeneration seen in aged mice is correlated with impaired c-Jun expression and phosphorylation following injury. These data provide a neurobiological explanation for the poor outcome associated with nerve repair in the aged. (C) 2012 Elsevier Inc. All rights reserved.
All Author(s) ListYuan QJ, Su HX, Guo JS, Tsang KY, Cheah KSE, Chiu K, Yang J, Wong WM, So KF, Huang JD, Wu WT, Lin ZX
Journal nameExperimental Gerontology
Volume Number47
Issue Number4
Pages329 - 336
LanguagesEnglish-United Kingdom
KeywordsAging; Axonal injury; Axonal regeneration; Motoneuron; Mouse; Transcription factor
Web of Science Subject CategoriesGeriatrics & Gerontology; GERIATRICS & GERONTOLOGY

Last updated on 2020-05-07 at 01:17