title: Effect of bFGF on neuronal damage induced by sequential treatment of amyloid β and excitatory amino acid in vitro and in vivo.
abstract: Effects of basic fibroblast growth factor (bFGF), a potent neurotrophin, on neuronal damage induced by sequential treatment of amyloid β (Aβ) peptide and excitatory amino acid were examined in vitro and in vivo. Treatment of rat primary cortical neurons with glutamate (10μM, 30μM) resulted in neuronal damage, and pretreatment of the neurons with Aβ(25-35) (1.0μM) at 48h before glutamate stimulation augmented the susceptibility of the cells to the glutamate-induced neurotoxicity. Application of bFGF (0.3, 1, 3ng/ml) and MK-801 (1, 3, 10, 30nM) to the culture at 24h before glutamate stimulation markedly decreased the neuronal damage elicited by Aβ(25-35) and glutamate. In a rat model of Alzheimer's disease, in which aggregated Aβ(1-40) (4μg/1μl) was injected into the hippocampus, followed by an injection of ibotenate (an NMDA receptor agonist, 0.3μg/0.5μl) into the same sites at 48h later, significant neuronal damage and learning deficit was induced. Administration of bFGF (25ng/1μl) into the hippocampus at 24h before ibotenate inhibited the neuronal damage and demonstrated a trend of attenuating spatial learning deficits. These results suggest that bFGF might be a useful agent for treatment of Alzheimer's disease in which Aβ peptide and glutamate would be involved as causative substances.
authors.affiliation: Asubio Pharma Co. Limited, 6-4-3 Minatojima-minamimachi, Chuo-ku, Kobe, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Noshita
authors.forename: Norihito
authors.initials: N
authors.lastname: Murayama
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Oka
authors.forename: Ryoko
authors.initials: R
authors.lastname: Ogino
authors.forename: Shizuo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Inoue
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007051:Ibotenic Acid / Q000633:toxicity; D007858:Learning / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D016222:Fibroblast Growth Factor 2; D007051:Ibotenic Acid; D018698:Glutamic Acid; D016291:Dizocilpine Maleate