Article: Decreased c-Jun expression correlates with impaired spinal motoneuron regeneration in aged mice following sciatic nerve crush

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TitleDecreased c-Jun expression correlates with impaired spinal motoneuron regeneration in aged mice following sciatic nerve crush
AuthorsYuan, Q1 3
Su, H1
Guo, J1
Tsang, KY1
Cheah, KSE1
Chiu, K1
Yang, J1
Wong, WM1
So, KF1 2
Huang, JD1
Wu, W1 2
Lin, ZX3
KeywordsAging
Axonal injury
Axonal regeneration
Motoneuron
Mouse
Transcription factor
Issue Date2012
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/expgero
CitationExperimental Gerontology, 2012, v. 47 n. 4, p. 329-336 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.exger.2012.02.006
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. © 2012 Elsevier Inc.
ISSN0531-5565
2011 Impact Factor: 3.741
2011 SCImago Journal Rankings: 0.273
DOIhttp://dx.doi.org/10.1016/j.exger.2012.02.006
ISI Accession Number IDWOS:000302624500007
Funding AgencyGrant Number
Chinese University of Hong Kong
University of Hong Kong
National Basic Research Program of China (973 program)2011CB504402
Hong Universities Grant CouncilAoE/M-04/04
Funding Information:

This study was supported by the Chinese University of Hong Kong, the University of Hong Kong and the National Basic Research Program of China (973 program; 2011CB504402). KY Tsang and KSE Cheah are supported by Hong Universities Grant Council project AoE/M-04/04. We thank Dr. IC Bruce of Zhejiang University School of Medicine for reading the manuscript.

ReferencesReferences in Scopus
GrantsDevelopmental genomics and skeletal research
DC Field
Value
dc.contributor.authorYuan, Q
dc.contributor.authorSu, H
dc.contributor.authorGuo, J
dc.contributor.authorTsang, KY
dc.contributor.authorCheah, KSE
dc.contributor.authorChiu, K
dc.contributor.authorYang, J
dc.contributor.authorWong, WM
dc.contributor.authorSo, KF
dc.contributor.authorHuang, JD
dc.contributor.authorWu, W
dc.contributor.authorLin, ZX
dc.date.accessioned2012-05-29T06:05:20Z
dc.date.available2012-05-29T06:05:20Z
dc.date.issued2012
dc.description.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. © 2012 Elsevier Inc.
dc.description.grantDevelopmental genomics and skeletal research
dc.description.grantcode44444
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationExperimental Gerontology, 2012, v. 47 n. 4, p. 329-336 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.exger.2012.02.006
dc.identifier.citeulike10397378
dc.identifier.doihttp://dx.doi.org/10.1016/j.exger.2012.02.006
dc.identifier.epage336
dc.identifier.hkuros199492
dc.identifier.hkuros210513
dc.identifier.isiWOS:000302624500007
Funding AgencyGrant Number
Chinese University of Hong Kong
University of Hong Kong
National Basic Research Program of China (973 program)2011CB504402
Hong Universities Grant CouncilAoE/M-04/04
Funding Information:

This study was supported by the Chinese University of Hong Kong, the University of Hong Kong and the National Basic Research Program of China (973 program; 2011CB504402). KY Tsang and KSE Cheah are supported by Hong Universities Grant Council project AoE/M-04/04. We thank Dr. IC Bruce of Zhejiang University School of Medicine for reading the manuscript.

dc.identifier.issn0531-5565
2011 Impact Factor: 3.741
2011 SCImago Journal Rankings: 0.273
dc.identifier.issue4
dc.identifier.pmid22382134
dc.identifier.scopuseid_2-s2.0-84862829326
dc.identifier.spage329
dc.identifier.urihttp://hdl.handle.net/10722/147661
dc.identifier.volume47
dc.languageeng
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/expgero
dc.publisher.placeUnited States
dc.relation.ispartofExperimental Gerontology
dc.relation.referencesReferences in Scopus
dc.subjectAging
dc.subjectAxonal injury
dc.subjectAxonal regeneration
dc.subjectMotoneuron
dc.subjectMouse
dc.subjectTranscription factor
dc.titleDecreased c-Jun expression correlates with impaired spinal motoneuron regeneration in aged mice following sciatic nerve crush
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. The University of Hong Kong
  3. Chinese University of Hong Kong