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Up‐regulation of brain‐derived neurotrophic factor by application of fibroblast growth factor‐2 to the cut optic nerve is important for long‐term survival of retinal ganglion cells
Author(s) -
Blanco Rosa E.,
Soto Ileana,
DupreyDíaz Mildred,
Blagburn Jonathan M.
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21793
Subject(s) - axotomy , tropomyosin receptor kinase b , neurotrophic factors , brain derived neurotrophic factor , biology , immunostaining , microbiology and biotechnology , fibroblast growth factor , neurotrophin , retinal ganglion cell , retina , basic fibroblast growth factor , neuroscience , endocrinology , medicine , growth factor , regeneration (biology) , receptor , immunology , immunohistochemistry , biochemistry
Application of basic fibroblast growth factor (FGF‐2) to the optic nerve after axotomy promotes the survival of retinal ganglion cells (RGCs) in the frog Rana pipiens and results in a rapid up‐regulation of brain‐derived neurotrophic factor (BDNF) and TrkB synthesis by the RGCs. Here we investigate whether this up‐regulation is maintained over the long term and whether it is required for FGF‐2's survival effect. At 6 weeks after axotomy and FGF‐2 treatment, we found more RGCs immunopositive for BDNF protein and higher intensity of BDNF and TrkB immunostaining, accompanied by increases in BDNF and TrkB mRNA in RGCs. Application of fluorescently labeled siRNA targeted against BDNF to the cut RGC axons showed that it was transported to the cell bodies. Axonal siRNA treatment eliminated the increases in BDNF immunostaining and mRNA that were induced by FGF‐2 and had no effect on TrkB mRNA. This reduction in BDNF synthesis by siRNA greatly reduced the long‐term survival effect of FGF‐2 on RGCs. This, taken together with previous results, suggests that, although FGF‐2 may initially activate survival pathways via ERK signaling, its main long‐term survival effects are mediated via its up‐regulation of BDNF synthesis by the RGCs. © 2008 Wiley‐Liss, Inc.