QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, February 16, 2005, 25(7):1645-1653; doi:10.1523/JNEUROSCI.3269-04.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (29) Citing Articles via Google Scholar Google Scholar Articles by Qiu, J. Articles by Thompson, S. W. N. Search for Related Content PubMed PubMed Citation Articles by Qiu, J. Articles by Thompson, S. W. N.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Conditioning Injury-Induced Spinal Axon Regeneration Requires Signal Transducer and Activator of Transcription 3 Activation

Jin Qiu, William B. J. Cafferty, Stephen B. McMahon, and Stephen W. N. Thompson

Wolfson Centre for Age-Related Diseases, Guy's, King's, and St. Thomas's School of Biomedical Science, King's College London, London SE1 1UL, United Kingdom

Sensory axons in the adult spinal cord do not regenerate after injury. This is essentially because of inhibitory components in the damaged CNS, such as myelin-associated inhibitors and the glial scar. However, if the sciatic nerve is axotomized before injury of the dorsal column, injured axons can regenerate a short distance in the spinal cord. Here, we show that sciatic nerve transection results in time-dependent phosphorylation and activation of the transcription factor, signal transducer and activator of transcription 3 (STAT3), in dorsal root ganglion (DRG) neurons. This effect is specific to peripheral injuries and does not occur when the dorsal column is crushed. Sustained perineural infusion of the Janus kinase 2 (JAK2) inhibitor AG490 to the proximal nerve stump can block STAT3 phosphorylation after sciatic nerve transection and results in reduced growth-associated protein 43 upregulation and compromised neurite outgrowth in vitro. Importantly, in vivo perineural infusion of AG490 also significantly attenuates dorsal column axonal regeneration in the adult spinal cord after a preconditioning sciatic nerve transection. We conclude that STAT3 activation is necessary for increased growth ability of DRG neurons and improved axonal regeneration in the spinal cord after a conditioning injury.

Key words: STAT; regeneration; condition lesion; gp130 cytokines; axon growth; sensory system

---

Received Aug 10, 2004; revised December 12, 2004; accepted December 16, 2004.

This article has been cited by other articles:

				S. Kiryu-Seo, R. Kato, T. Ogawa, S. Nakagomi, K. Nagata, and H. Kiyama Neuronal Injury-inducible Gene Is Synergistically Regulated by ATF3, c-Jun, and STAT3 through the Interaction with Sp1 in Damaged Neurons J. Biol. Chem., March 14, 2008; 283(11): 6988 - 6996. [Abstract] [Full Text] [PDF]

				M. A. Ozog, G. Modha, J. Church, R. Reilly, and C. C. Naus Co-administration of Ciliary Neurotrophic Factor with Its Soluble Receptor Protects against Neuronal Death and Enhances Neurite Outgrowth J. Biol. Chem., March 7, 2008; 283(10): 6546 - 6560. [Abstract] [Full Text] [PDF]

				A. Muller, T. G. Hauk, and D. Fischer Astrocyte-derived CNTF switches mature RGCs to a regenerative state following inflammatory stimulation Brain, December 1, 2007; 130(12): 3308 - 3320. [Abstract] [Full Text] [PDF]

				R. Seijffers, C. D. Mills, and C. J. Woolf ATF3 Increases the Intrinsic Growth State of DRG Neurons to Enhance Peripheral Nerve Regeneration J. Neurosci., July 25, 2007; 27(30): 7911 - 7920. [Abstract] [Full Text] [PDF]

				S. Pieraut, V. Laurent-Matha, C. Sar, T. Hubert, I. Mechaly, C. Hilaire, M. Mersel, E. Delpire, J. Valmier, and F. Scamps NKCC1 Phosphorylation Stimulates Neurite Growth of Injured Adult Sensory Neurons J. Neurosci., June 20, 2007; 27(25): 6751 - 6759. [Abstract] [Full Text] [PDF]

				R. K. Monroe and S. W. Halvorsen Mercury Abolishes Neurotrophic Factor-Stimulated Jak-STAT Signaling in Nerve Cells by Oxidative Stress Toxicol. Sci., November 1, 2006; 94(1): 129 - 138. [Abstract] [Full Text] [PDF]

				Y. P. Ng, Z. H. Cheung, and N. Y. Ip STAT3 as a Downstream Mediator of Trk Signaling and Functions J. Biol. Chem., June 9, 2006; 281(23): 15636 - 15644. [Abstract] [Full Text] [PDF]

				M. P. Steinmetz, K. P. Horn, V. J. Tom, J. H. Miller, S. A. Busch, D. Nair, D. J. Silver, and J. Silver Chronic Enhancement of the Intrinsic Growth Capacity of Sensory Neurons Combined with the Degradation of Inhibitory Proteoglycans Allows Functional Regeneration of Sensory Axons through the Dorsal Root Entry Zone in the Mammalian Spinal Cord J. Neurosci., August 31, 2005; 25(35): 8066 - 8076. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help