A beta oligomers inhibit synapse remodelling necessary for memory consolidation

作者:Freir Darragh B; Fedriani Rocio; Scully Darren; Smith Imelda M; Selkoe Dennis J; Walsh Dominic M*; Regan Ciaran M
来源:Neurobiology of Aging, 2011, 32(12): 2211-2218.
DOI:10.1016/j.neurobiolaging.2010.01.001

摘要

Extensive research has implicated the amyloid-beta protein (A beta) 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 A beta production is associated with impaired learning and/or recall. Here we examined the effects of cell-derived SDS-stable 7PA2-derived soluble A beta oligomers on consolidation of avoidance learning. At 0, 3, 6, 9 or 12 h after training, animals received an intracerebroventricular injection of A beta-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 A beta at 6 or 9 h post-training showed a significant impairment in memory consolidation at 48 h. Importantly, impaired animals injected at 9 h had significantly fewer synapses in the dentate gyrus. These data suggest that A beta low-n oligomers target specific temporal facets of consolidation-associated synaptic remodelling whereby loss of functional synapses results in impaired consolidation.

  • 出版日期2011-12