CONICET | Buscador de Institutos y Recursos Humanos

Amyloid b peptide (Ab) is considered one of the main agents of Alzheimers disease pathogenesis. Recently, it has been proposed that memory deficits are caused by different stages of Ab aggregation, particularly by oligomers. In addition, although memory impairment was found after Ab administration in rodents and chicks, the nature of the memory deficits induced in invertebrates by acute administration of mammalian Ab peptides is not well understood. Previously, we reported the amnesic effect of acute pre-training administration of naturally formed fibrils (NF) in crab memory. Here we evaluate the effect of NF and synthetic Ab peptides administration at different times before and after training in this well characterized invertebrate memory model, the context-signal memory of the crab Chasmagnathus. We found a clear amnesic effect at very low doses of naturally Ab NF only when administered immediately pre-and post-training, but not 24 h and 18 h before or 6 h after training. Activation of ERK/MAPK (a protein kinase required for memory formation in this model) 60 min after administration was found. In contrast, neither JNK/SAPK nor NF-kB transcription factor were activated. Furthermore, synthetic Ab1-42 and Abpy3-42 administration induced amnesia when used after a protocol for fibrillation but not after a protocol for oligomerization. On the contrary, no amnestic effect was found when fibrillated Ab1-40 and Abpy11-42 peptides were used. Thus, Ab1-42 and Ab3-42 peptides impaired memory and the effects were only found when highly aggregated peptides, which may include fibrils, protofibrils and oligomers, were administered. These temporally- and signaling-specific effects suggest that Ab impairs memory by inducing transient physiological, rather than permanent neuropathological, alterations of the brain and this effect is achieved through generalized ERK activation.