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Aβ oligomers inhibit synapse remodelling necessary for memory consolidation

Aβ oligomers inhibit synapse remodelling necessary for memory consolidation,10.1016/j.neurobiolaging.2010.01.001,Neurobiology of Aging,Darragh B. Frei

Aβ oligomers inhibit synapse remodelling necessary for memory consolidation   (Citations: 3)
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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.
Journal: Neurobiology of Aging - NEUROBIOL AGING , vol. 32, no. 12, pp. 2211-2218, 2011
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    • ..., which suggests that the specific impairment of contextual fear memory in our study was caused by Abeta oligomers that diffused from the ventricle into the hippocampus. Accordingly, previous studies found that injection of natural Abeta oligomers into the lateral ventricle impaired synapse remodeling in the hippocampus ...

    Kara A. Kittelbergeret al. Natural Amyloid-Beta Oligomers Acutely Impair the Formation of a Conte...

    • ...Single intracerebral ventricular (i.c.v.) infusions into adult rat brain of either Abd/t from 7PA2 cells or Ab dimer from AD brain caused transient memory and learning deficits [19-21,23,24]...
    • ...Infusion (i.c.v.) of Abd/t into adult rat brain several hours after training inhibits synaptic remodeling that accompanies learning and memory consolidation by preventing a transient increase in the number of synapses in the dentate gyrus [24]...
    • ...This value for Abd/t concentration is close to that estimated from the Abd/t immunostaining on Western blots after epitope exposure by boiling the membrane [20], and is also quite similar to the concentration of Abd/t in 7PA2 medium estimated by Freir et al. [24]...
    • ...Injection of single doses of Abd/ t-containing medium into brains of adult rats also leads to defects in associative memory and to memory consolidation with a striking inhibition of the synaptic increases that occur during memory consolidation in the dentate gyrus [24]...

    Richard C Daviset al. Amyloid beta dimers/trimers potently induce cofilin-actin rods that ar...

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