title: NMDA-receptor activation but not ion flux is required for amyloid-beta induced synaptic depression.
abstract: Alzheimer disease is characterized by a gradual decrease of synaptic function and, ultimately, by neuronal loss. There is considerable evidence supporting the involvement of oligomeric amyloid-beta (Aβ) in the etiology of Alzheimer's disease. Historically, AD research has mainly focused on the long-term changes caused by Aβ rather than analyzing its immediate effects. Here we show that acute perfusion of hippocampal slice cultures with oligomeric Aβ depresses synaptic transmission within 20 minutes. This depression is dependent on synaptic stimulation and the activation of NMDA-receptors, but not on NMDA-receptor mediated ion flux. It, therefore, appears that Aβ dependent synaptic depression is mediated through a use-dependent metabotropic-like mechanism of the NMDA-receptor, but does not involve NMDA-receptor mediated synaptic transmission, i.e. it is independent of calcium flux through the NMDA-receptor.
authors.affiliation: Département de Physiologie, Groupe de Recherche sur le Système Nerveux Central, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Albert
authors.initials: A
authors.lastname: Tamburri
authors.forename: Anthony
authors.initials: A
authors.lastname: Dudilot
authors.forename: Sara
authors.initials: S
authors.lastname: Licea
authors.forename: Catherine
authors.initials: C
authors.lastname: Bourgeois
authors.forename: Jannic
authors.initials: J
authors.lastname: Boehm
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D017136:Ion Transport; D009433:Neural Inhibition / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; C075222:amyloid beta-protein (1-42); D018698:Glutamic Acid