Effect on memory of acute administration of naturally secreted fibrils and synthetic amyloid-beta peptides in an invertebrate model

FELD M; GALLI C; PICCINI A; ROMANO A

NEUROBIOLOGY OF LEARNING AND MEMORY

Academic Press

Lugar: Estados Unidos; Año: 2008 vol. 89 p. 407 - 418

1074-7427

Amyloid beta peptide (Abeta) is considered one of the main agents of Alzheimer´s disease pathogenesis. Recently, it has been proposed that memory deficits are caused by different stages of Abeta aggregation, particularly by oligomers. In addition, although memory impairment was found after Abeta administration in rodents and chicks, the nature of the memory deficits induced in invertebrates by acute administration of mammalian Abeta 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 Abeta 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 Abeta NF only when administered immediately pre- and post-training, but not 24h and 18h before or 6h after training. Activation of ERK/MAPK (a protein kinase required for memory formation in this model) 60min after administration was found. In contrast, neither JNK/SAPK nor NF-kappaB transcription factor were activated. Furthermore, synthetic Abeta1-42 and Abetapy3-42 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 Abeta1-40 and Abetapy11-42 peptides were used. Thus, Abeta1-42 and Abetapy3-42 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 Abeta impairs memory by inducing transient physiological, rather than permanent neuropathological, alterations of the brain and this effect is achieved through generalized ERK activation.