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PMID: 20005819 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

SOCS3 deletion promotes optic nerve regeneration in vivo.

Neuron ·Vol. 64 ·No. 5 ·2009-12-10 ·Pages 617-23

Smith PD, Sun F, Park KK, Cai B, Wang C, Kuwako K, Martinez-Carrasco I, Connolly L, He Z

Abstract

Axon regeneration failure accounts for permanent functional deficits following CNS injury in adult mammals. However, the underlying mechanisms remain elusive. In analyzing axon regeneration in different mutant mouse lines, we discovered that deletion of suppressor of cytokine signaling 3 (SOCS3) in adult retinal ganglion cells (RGCs) promotes robust regeneration of injured optic nerve axons. This regeneration-promoting effect is efficiently blocked in SOCS3-gp130 double-knockout mice, suggesting that SOCS3 deletion promotes axon regeneration via a gp130-dependent pathway. Consistently, a transient upregulation of ciliary neurotrophic factor (CNTF) was observed within the retina following optic nerve injury. Intravitreal application of CNTF further enhances axon regeneration from SOCS3-deleted RGCs. Together, our results suggest that compromised responsiveness to injury-induced growth factors in mature neurons contributes significantly to regeneration failure. Thus, developing strategies to modulate negative signaling regulators may be an efficient strategy of promoting axon regeneration after CNS injury.

MeSH Terms
Analysis of Variance Animals Animals, Newborn Axons/drug effects,metabolism,pathology Carrier Proteins/metabolism Cholera Toxin/metabolism Ciliary Neurotrophic Factor/genetics,pharmacology Cytokine Receptor gp130/deficiency Disease Models, Animal Dose-Response Relationship, Drug Gene Expression Regulation/genetics Green Fluorescent Proteins/genetics Injections, Intraventricular/methods Mice Mice, Inbred C57BL Mice, Transgenic Nerve Regeneration/drug effects,genetics,physiology Optic Nerve Injuries/drug therapy,genetics,physiopathology Organ Culture Techniques Phosphotransferases (Alcohol Group Acceptor)/metabolism Retinal Ganglion Cells/pathology,physiology Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins/deficiency,physiology TOR Serine-Threonine Kinases Time Factors Tubulin/metabolism
Chemicals
Carrier Proteins Ciliary Neurotrophic Factor Il6st protein, mouse Socs3 protein, mouse Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins Tubulin beta3 tubulin, mouse Cytokine Receptor gp130 Green Fluorescent Proteins Cholera Toxin Phosphotransferases (Alcohol Group Acceptor) mTOR protein, mouse TOR Serine-Threonine Kinases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Smith Patrice D
F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Sun Fang
Park Kevin Kyungsuk
Cai Bin
Wang Chen
Kuwako Kenichiro
Martinez-Carrasco Irene
Connolly Lauren
He Zhigang
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2009.11.021
Published
2009-12-10
Pages
617-23
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC2796263
Subset
IM
Grants
NINDS NIH HHS · R01 NS051788 · United States
NINDS NIH HHS · R01 NS051788-04 · United States
CIHR · Canada
Corrections
CommentIn
PMID: 20005813
External Links
PubMed source DOI: 10.1016/j.neuron.2009.11.021 PMC Full Text View journal details
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