title: Soluble Aβ(1-40) peptide increases excitatory neurotransmission and induces epileptiform activity in hippocampal neurons.
abstract: It is believed that amyloid-β peptide (Aβ), in its aggregated-oligomeric state, constitutes one of the neurotoxic factors involved in the pathogenesis of Alzheimer's disease. With the objective of studying a potential role of the peptide on synaptic transmission, we studied the effect of soluble Aβ(1-40) on synaptic transmission in rat hippocampal neurons. Neurons incubated with 500 nM of Aβ(1-40) peptide for 3 days presented higher levels of intracellular calcium transients, as evaluated by fluorimetric techniques. These effects of Aβ were time and concentration dependent and were accompanied by increases in glutamatergic (0.8±0.2 Hz to 2.9±0.6 Hz), but not GABAergic, transmission. The analysis of pharmacologically isolated currents in treated neurons showed increases in both AMPA- and NMDA-mediated currents as compared to control. The effects of the peptide on the frequency of synaptic currents correlated well with increases in the number of SV2 puncta and of FM1-43 destaining, suggesting a presynaptic locus for the peptide. The data also shows that application of either Aβ or bicuculline alone for 24 h was without effects on neurotransmission. However, their co-application induced an increase in synaptic transmission which was accompanied by synchronous discharges reminiscent to those produced by pro-convulsive drugs, such as bicuculline. In conclusion, these results suggest that the soluble form of Aβ(1-40) participates in the regulation of synaptic transmission increasing excitability and producing a pre-epileptogenic state in hippocampal neurons.
authors.affiliation: Laboratory of Neurophysiology, Department of Physiology, University of Concepción, Concepción, Chile.
authors.forename: Magdalena E
authors.initials: ME
authors.lastname: Cuevas
authors.forename: Henny
authors.initials: H
authors.lastname: Haensgen
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Sepúlveda
authors.forename: Gabriela
authors.initials: G
authors.lastname: Zegers
authors.forename: Jorge
authors.initials: J
authors.lastname: Roa
authors.forename: Carlos
authors.initials: C
authors.lastname: Opazo
authors.forename: Luis G
authors.initials: LG
authors.lastname: Aguayo
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)