Fibroblast growth factor-5 promotes differentiation of cultured rat septal cholinergic and raphe serotonergic neurons: comparison with the effects of neurotrophins.
Fibroblast growth factor-5 (FGF-5) is a member of the fibroblast growth factor gene family, which has a signal sequence characteristic of secretory proteins. FGF-5 mRNA has previously been shown to be present in the adult mouse brain. Here we demonstrate that recombinant FGF-5 has neurotrophic activity on cultured rat septal cholinergic and raphe serotonergic neurons. The effect of FGF-5 on serotonin uptake was stronger than that evoked with either brain-derived neurotrophic factor or neurotrophin-3. FGF-5 also increased the choline acetyltransferase activity of cultured rat septal cholinergic neurons, the effect being additive to that of nerve growth factor. In situ hybridization experiments and immunohistochemistry using a specific anti-FGF-5 antibody demonstrated that FGF-5 is expressed in rat hippocampal neurons. Like nerve growth factor mRNA, the levels of FGF-5 mRNA in the rat hippocampus increased substantially during early postnatal development. In addition, injection of the muscarinic receptor agonist pilocarpine elevated FGF-5 mRNA. The presence of the secretory FGF-5 in the rat hippocampus, a target field of septal cholinergic and raphe serotonergic neurons, suggests that FGF-5 acts as a trophic factor for these neurons also in vivo.
Lindholm
D
D
Department of Neurochemistry, Max Planck Institute for Psychiatry, Planegg-Martinsried, FRG.
Harikka
J
J
da Penha Berzaghi
M
M
Castrén
E
E
Tzimagiorgis
G
G
Hughes
R A
RA
Thoenen
H
H
D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004622:Embryo, Mammalian; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors / Q000096:biosynthesis* / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020933:Neurotrophin 3; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*
C496449:FGF5 protein, human; C496450:Fgf5 protein, mouse; C496451:Fgf5 protein, rat; D006133:Growth Substances; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D051521:Fibroblast Growth Factor 5; D012701:Serotonin; D005346:Fibroblast Growth Factors; D002795:Choline O-Acetyltransferase