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

Journal of Neuroscience Research
Rosa E BlancoJonathan Blagburn

Abstract

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.

References

Oct 27, 1995·Science·H Thoenen
Jul 1, 1995·Current Biology : CB·A M Davies, E M Wright
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·Z KokaiaO Lindvall
Jan 1, 1996·Seikagaku. The Journal of Japanese Biochemical Society·Y FurukawaK Hayashi
Jan 1, 1996·Annual Review of Neuroscience·G R Lewin, Y A Barde
Jul 10, 1999·Neuron·Hadley Wilson HorchLawrence C Katz
Oct 9, 2002·Nature Neuroscience·Hadley Wilson Horch, Lawrence C Katz
Sep 26, 2003·Investigative Ophthalmology & Visual Science·Keith R G MartinWilliam W Hauswirth
Jun 19, 2004·Reviews in the Neurosciences·Hadley Wilson Horch
Sep 24, 2004·Experimental Neurology·Irina KiprianovaKlaus Unsicker
May 10, 2006·RNA·Yuriy FedorovAnastasia Khvorova

Citations

Sep 4, 2012·Journal of Chemical Neuroanatomy·Mildred V Duprey-DíazRosa E Blanco
Jun 1, 2016·Journal of Chemical Neuroanatomy·Mildred V Duprey-DíazRosa E Blanco
Jan 3, 2013·Journal of Neurochemistry·Sebok Kumar HalderHiroshi Ueda
Jul 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Spyros MerkourisJia Xie

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