Fibroblast growth factor 2 applied to the optic nerve after axotomy up-regulates BDNF and TrkB in ganglion cells by activating the ERK and PKA signaling pathways

Ileana Soto, Joshua J.C. Rosenthal, Jonathan M. Blagburn, Rosa E. Blanco

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47 Scopus citations

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. Here we investigate the effects of FGF-2 treatment upon the synthesis of brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine receptor kinase B (TrkB). Axotomy alone increased the amounts of BDNF and TrkB mRNA in RGCs after 1 week and 48 h, respectively; FGF-2 treatment to the nerve accelerated and increased this up-regulation of both. FGF-2 also increased the amounts of phosphorylated cAMP response element binding protein (pCREB) in the retina. Blocking extracellular-regulated kinase (ERK) activation with PD98059 or U0126 prevented the FGF-2-induced up-regulation of BDNF transcription but had no effect on TrkB. However, blocking protein kinase A (PKA) with H89 or Rp-8-Cl-cAMPS reduced the up-regulation of both BDNF and TrkB, and reduced pCREB. In addition, H89 inhibited ERK activation, indicating cross-talk between the pathways. Finally, axonal application of blocking antibody against the FGF receptor 1 (FGFR1) prevented the FGF-2-induced up-regulation of BDNF and TrkB. Our results suggest that FGF-2 acts on RGCs via FGFR1, activating the ERK pathway and CREB to increase BDNF synthesis, and PKA and CREB to increase TrkB synthesis.

Original languageEnglish (US)
Pages (from-to)82-96
Number of pages15
JournalJournal of Neurochemistry
Volume96
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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