Premium
Preferential neurotrophic activity of fibroblast growth factor‐20 for dopaminergic neurons through fibroblast growth factor receptor‐1c
Author(s) -
Ohmachi Shigeki,
Mikami Tadahisa,
Konishi Morichika,
Miyake Ayumi,
Itoh Nobuyuki
Publication year - 2003
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.10592
Subject(s) - pars compacta , substantia nigra , dopaminergic , neurotrophic factors , neurotrophin , fibroblast growth factor , biology , glial cell line derived neurotrophic factor , mapk/erk pathway , fibroblast growth factor receptor , microbiology and biotechnology , neuroscience , endocrinology , medicine , signal transduction , receptor , dopamine , biochemistry
Abstract Degeneration of dopaminergic neurons of the substantia nigra causes Parkinson's disease. Therefore, neurotrophic factors for dopaminergic neurons are of substantial clinical interest. Fibroblast growth factor (FGF)‐20 preferentially expressed in the substantia nigra pars compacta (SNPC) of the rat brain significantly enhanced the survival of midbrain dopaminergic neurons. Here we examined the mechanism of action of FGF‐20 on dopaminergic neurons. FGF‐20 slightly enhanced the survival of total neurons of the midbrain, indicating that it preferentially enhanced the survival of dopaminergic neurons. FGF receptor (FGFR)‐1c was found to be expressed abundantly in dopaminergic neurons in the SNPC but at much lower levels in neurons of other midbrain regions by in situ hybridization. FGF‐20 was also found to bind FGFR‐1c with high affinity with the BIAcore system. Furthermore, FGF‐20 activated the mitogen‐activated protein kinase (MAPK) pathway, which is the major intracellular signaling pathway of FGFs. Both the FGFR‐1 inhibitor SU5402 and the MAPK pathway inhibitor PD98059 also significantly inhibited the activation of the MAPK pathway by FGF‐20 and the neurotrophic activity of FGF‐20. The present findings indicate that the activation of the MAPK pathway by FGF‐20 signaling through FGFR‐1c plays important roles in the survival of dopaminergic neurons in the SNPC. © 2003 Wiley‐Liss, Inc.