Fibroblast growth factor-2 increases functional excitatory synapses on hippocampal neurons.
The effect of fibroblast growth factor-2 (FGF-2) on synapse formation was investigated using rat cultured hippocampal neurons. Treatment with FGF-2 (0.4-10 ng/mL) for 6 days enhanced synaptogenesis on these neurons by approximately 50%, as determined by counting puncta immunostained for presynaptic- or postsynaptic-specific proteins. This enhancement was statistically significant, and was abolished by a specific inhibitor of mitogen-activated protein kinase (MAPK). The majority of neurons expressed FGF receptors (types 1-3) abundantly on the membrane of somata, dendrites, and growth cones, and in these regions phosphorylation of MAPK was enhanced after FGF-2 application. Furthermore, our experiments showed that the majority of synapses formed in cultures containing FGF-2 were positive both for presynaptic proteins and postsynaptic excitatory synapse-specific proteins, and that these synapses had a similar capacity to recycle the fluorescent styryl dye FM4-64 as those in the control culture. These results indicate that: (i) FGF-2 increases excitatory synapses on hippocampal neurons by activating MAPK activity through FGF receptors; and (ii) synapses formed in FGF-2-treated culture are capable of cycling vesicles.
Li
Ai-Jun
AJ
Age Dimension Research Centre, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Suzuki
Seigo
S
Suzuki
Masashi
M
Mizukoshi
Eiichi
E
Imamura
Toru
T
D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism
D017468:Receptors, Fibroblast Growth Factor; D016704:Synapsins; D016708:Synaptophysin; D016222:Fibroblast Growth Factor 2; D020928:Mitogen-Activated Protein Kinases