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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2002-5-20
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3977-86
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12019317-Animals,
pubmed-meshheading:12019317-Axotomy,
pubmed-meshheading:12019317-Cell Death,
pubmed-meshheading:12019317-Cell Survival,
pubmed-meshheading:12019317-Cytoprotection,
pubmed-meshheading:12019317-Dependovirus,
pubmed-meshheading:12019317-Down-Regulation,
pubmed-meshheading:12019317-Enzyme Activation,
pubmed-meshheading:12019317-Enzyme Inhibitors,
pubmed-meshheading:12019317-Female,
pubmed-meshheading:12019317-Gene Transfer, Horizontal,
pubmed-meshheading:12019317-Genetic Vectors,
pubmed-meshheading:12019317-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12019317-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12019317-Proto-Oncogene Proteins,
pubmed-meshheading:12019317-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:12019317-RNA, Messenger,
pubmed-meshheading:12019317-Rats,
pubmed-meshheading:12019317-Rats, Sprague-Dawley,
pubmed-meshheading:12019317-Receptor, trkB,
pubmed-meshheading:12019317-Retinal Ganglion Cells,
pubmed-meshheading:12019317-Signal Transduction,
pubmed-meshheading:12019317-Up-Regulation
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pubmed:year |
2002
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pubmed:articleTitle |
TrkB gene transfer protects retinal ganglion cells from axotomy-induced death in vivo.
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pubmed:affiliation |
Department of Pathology and Cell Biology, Université de Montréal, Montreal, Quebec H3T 1J4, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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