title: Aβ oligomers inhibit synapse remodelling necessary for memory consolidation.
abstract: Extensive research has implicated the amyloid-β protein (Aβ) in the aetiology of Alzheimer's disease (AD). This protein has been shown to produce memory deficits when injected into rodent brain and in mouse models of AD Aβ production is associated with impaired learning and/or recall. Here we examined the effects of cell-derived SDS-stable 7PA2-derived soluble Aβ oligomers on consolidation of avoidance learning. At 0, 3, 6, 9 or 12h after training, animals received an intracerebroventricular injection of Aβ-containing or control media and recall was tested at 24 and 48 h. Immediately after 48 h recall animals were transcardially perfused and the brain removed for sectioning and EM analysis. Rats receiving injections of Aβ at 6 or 9h post-training showed a significant impairment in memory consolidation at 48 h. Importantly, impaired animals injected at 9h had significantly fewer synapses in the dentate gyrus. These data suggest that Aβ low-n oligomers target specific temporal facets of consolidation-associated synaptic remodelling whereby loss of functional synapses results in impaired consolidation.
authors.affiliation: Laboratory for Neurodegenerative Research, University College Dublin, Dublin, Ireland.
authors.forename: Darragh B
authors.initials: DB
authors.lastname: Freir
authors.forename: Rocio
authors.initials: R
authors.lastname: Fedriani
authors.forename: Darren
authors.initials: D
authors.lastname: Scully
authors.forename: Imelda M
authors.initials: IM
authors.lastname: Smith
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Selkoe
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Walsh
authors.forename: Ciaran M
authors.initials: CM
authors.lastname: Regan
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides