Journal
JOURNAL OF NEUROSCIENCE
Volume 22, Issue 10, Pages 3977-3986Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.22-10-03977.2002
Keywords
retinal ganglion cells; axotomy; gene transfer; TrkB; MAP kinase; cell survival
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Funding
- NEI NIH HHS [EY11123, R01 EY011123] Funding Source: Medline
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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 similar to50% 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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