title: Decreased c-Jun expression correlates with impaired spinal motoneuron regeneration in aged mice following sciatic nerve crush.
abstract: Post-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.
authors.affiliation: School of Chinese Medicine, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong SAR, China.
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Yuan
authors.forename: Huanxing
authors.initials: H
authors.lastname: Su
authors.forename: Jiasong
authors.initials: J
authors.lastname: Guo
authors.forename: Kwok Yeung
authors.initials: KY
authors.lastname: Tsang
authors.forename: Kathryn S E
authors.initials: KS
authors.lastname: Cheah
authors.forename: Kin
authors.initials: K
authors.lastname: Chiu
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Wai-Man
authors.initials: WM
authors.lastname: Wong
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Huang
authors.forename: Wutian
authors.initials: W
authors.lastname: Wu
authors.forename: Zhi-xiu
authors.initials: ZX
authors.lastname: Lin
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology*; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D012584:Sciatic Nerve / Q000293:injuries* / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000502:physiology
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger