Premium
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
Author(s) -
Soto Ileana,
Rosenthal Joshua J. C.,
Blagburn Jonathan M.,
Blanco Rosa E.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03510.x
Subject(s) - tropomyosin receptor kinase b , axotomy , tropomyosin receptor kinase a , neurotrophic factors , creb , brain derived neurotrophic factor , mapk/erk pathway , endocrinology , neurotrophin , medicine , microbiology and biotechnology , fibroblast growth factor , chemistry , basic fibroblast growth factor , tropomyosin receptor kinase c , biology , signal transduction , receptor , growth factor , transcription factor , central nervous system , biochemistry , platelet derived growth factor receptor , gene
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.