Molecular basis of beta-amyloid efect on memory formation in a triple transgenic mouse model

FELD M; BOCCIA MM; BLAKE MG; KRAWCZYK M; BARATTI CM; ROMANO A

Huerta Grande, Córdoba

Congreso; XXVI Reunión Anual de la SAN; 2011

SAN

Beta-amyloid peptide (βA) is the main component of neuritic plaques found in brains from Alzheimer Disease (AD) patients, clinically featured by cognitive impairment and progressive memory loss. βA activates memory-involved signaling pathways, such as ERK/MAPK, among others. These effects have shown to be dependent on the type of peptide, its concentration, time of exposition and its aggregation state. However the nature of the mnesic effect is still unclear. To study neurobiological mechanisms related to initial states of AD, in which a subtle deregulation of the physiologic function of βA can be inferred, we evaluated triple-transgenic (3xTg) mice memory in novel object recognition (NOR) task. 3xTg mice developed memory deficits between 3 and 6 months of age in correlation with ERK/MAPK activation specifically in prefrontal cortex (PFC). Here, we studied the correlation between MAPKs activation, βA effect on memory formation and the aggregation level of the peptide. We found extra-nuclear ERK/MAPK activation at 3 months and nuclear activation at 6 months of age in PFC, but no activation in hippocampus. The results support that the memory deficit found in 3xTg mice is dependent, at least in part, on βA accumulation and aggregation in prefrontal cortex.