Aβ oligomers inhibit synapse remodelling necessary for memory consolidation
Received 19 October 2009; received in revised form 22 December 2009; accepted 4 January 2010. published online 25 January 2010. Corrected Proof
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 48h. Immediately after 48h 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 48h. 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.
aLaboratory for Neurodegenerative Research, Ireland
bApplied Neurotherapeutics Research Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
cCenter for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA
Corresponding authors at: The Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. Tel.: +353 1 7166751; fax: +353 1 7166805.