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

FELD, MARIANA; KRAWCZYK, MARÍA; BOCCIA, MARIANO; ROMANO, ARTURO

Huerta Grande, Córdoba

Congreso; SAN 2011; 2011

Sociedad Argentina de Investigaciones en Neurociencias

Beta-amyloid peptide (βA) is the main component of neuritic plaques found in postmortem brain biopsies from Alzheimer Disease (AD) patients. AD is clinically featured by cognitive impairment and progressive memory loss at the beginning that gets worse and eventually incapacitating in pathologic advanced states. βA is capable of activating memory-involved signaling pathways, such as ERK/MAPK and nuclear factor kappa B (NF-kB), among others. This activation and the mnesic effect has shown to be dependent on the type of peptide, its concentration, the type of exposition and its aggregation state. Previous work with crabs from our group has suggested ERK/MAPK could be fine tuned by aggregated βA injection (Feld et al., 2008). However the nature of the mnesic effect is still unknown. To study neurobiological mechanisms related to initial states of AD, in which a subtle deregulation of the physiologic function of βA can be inferred and correlated to the cognitive impairment; we evaluated triple-transgenic (3xTg) and wild type mice memory in novel object recognition task (NOR). Recently, we have shown that 3xTg mice develop memory deficits between 3 and 6 months of age, and the deficit correlates 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.