PMID- 18655198 OWN - NLM STAT- MEDLINE DCOM- 20090122 LR - 20240415 IS - 1097-4547 (Electronic) IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 86 IP - 15 DP - 2008 Nov 15 TI - 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. PG - 3382-92 LID - 10.1002/jnr.21793 [doi] AB - 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. FAU - Blanco, Rosa E AU - Blanco RE AD - Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, Old San Juan, Puerto Rico. rblanco@rcm.upr.edu FAU - Soto, Ileana AU - Soto I FAU - Duprey-Diaz, Mildred AU - Duprey-Diaz M FAU - Blagburn, Jonathan M AU - Blagburn JM LA - eng GR - G12 RR003051/RR/NCRR NIH HHS/United States GR - S06 GM008224/GM/NIGMS NIH HHS/United States GR - S06 GM08224/GM/NIGMS NIH HHS/United States GR - G12RR-03051/RR/NCRR NIH HHS/United States GR - G12 MD007600/MD/NIMHD NIH HHS/United States GR - S06 GM008224-230039/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Axotomy MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cell Survival/physiology MH - Fibroblast Growth Factor 2/*metabolism MH - Immunohistochemistry MH - In Situ Hybridization MH - Optic Nerve/*metabolism/pathology MH - RNA, Messenger/analysis MH - RNA, Small Interfering MH - Rana pipiens MH - Receptor, trkB/metabolism MH - Retinal Ganglion Cells/*metabolism/pathology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Up-Regulation PMC - PMC2587377 MID - NIHMS55923 EDAT- 2008/07/26 09:00 MHDA- 2009/01/23 09:00 PMCR- 2009/11/15 CRDT- 2008/07/26 09:00 PHST- 2008/07/26 09:00 [pubmed] PHST- 2009/01/23 09:00 [medline] PHST- 2008/07/26 09:00 [entrez] PHST- 2009/11/15 00:00 [pmc-release] AID - 10.1002/jnr.21793 [doi] PST - ppublish SO - J Neurosci Res. 2008 Nov 15;86(15):3382-92. doi: 10.1002/jnr.21793.