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PMID: 12019317 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

TrkB gene transfer protects retinal ganglion cells from axotomy-induced death in vivo.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 22 ·No. 10 ·2002-05-15 ·Pages 3977-86

Cheng L, Sapieha P, Kittlerova P, Hauswirth WW, Di Polo A

Abstract

Injury-induced downregulation of neurotrophin receptors may limit the response of neurons to trophic factors, compromising their ability to survive. We tested this hypothesis in a model of CNS injury: retinal ganglion cell (RGC) death after transection of the adult rat optic nerve. TrkB mRNA rapidly decreased in axotomized RGCs to approximately 50% of the level in intact retinas. TrkB gene transfer into RGCs combined with exogenous BDNF administration markedly increased neuronal survival: 76% of RGCs remained alive at 2 weeks after axotomy, a time when >90% of these neurons are lost without treatment. Activation of mitogen-activated protein kinase, but not phosphatidylinositol-3 kinase, was required for TrkB-induced survival. These data provide proof-of-principle that enhancing the capacity of injured neurons to respond to trophic factors can be an effective neuroprotective strategy in the adult CNS.

MeSH Terms
Animals Axotomy Cell Death/drug effects,physiology Cell Survival/physiology Cytoprotection/drug effects,physiology Dependovirus/genetics Down-Regulation/physiology Enzyme Activation/drug effects Enzyme Inhibitors/pharmacology Female Gene Transfer, Horizontal Genetic Vectors Mitogen-Activated Protein Kinases/metabolism Protein Serine-Threonine Kinases Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-akt RNA, Messenger/metabolism Rats Rats, Sprague-Dawley Receptor, trkB/genetics,metabolism Retinal Ganglion Cells/cytology,drug effects,metabolism Signal Transduction/drug effects,physiology Up-Regulation/physiology
Chemicals
Enzyme Inhibitors Proto-Oncogene Proteins RNA, Messenger Receptor, trkB Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Mitogen-Activated Protein Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cheng Li
Department of Pathology and Cell Biology, Université de Montréal, Montreal, Quebec H3T 1J4, Canada.
Sapieha Przemyslaw
Kittlerova Pavla
Hauswirth William W
Di Polo Adriana
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
20026382
Published
2002-05-15
Pages
3977-86
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6757661
Subset
IM
Grants
NEI NIH HHS · R01 EY011123 · United States
NEI NIH HHS · EY11123 · United States
External Links
PubMed source DOI: 20026382 PMC Full Text View journal details
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