Behavioral and molecular characterization of a triple transgenic mouse model of Alzheimer’s disease

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

Los Cocos, Córdoba

Simposio; SISTAM 2010; 2010

Alzheimer’s disease (AD) is clinically characterized by progressive memory decline and cognitive dysfunction. Senile plaques containing mainly amyloid-β peptides, neurofibrillary tangles composed of hyperphosphorylated tau and neuronal loss are its major histological features. However, Aβ are elevated without plaque formation or nerve cell loss, yet learning and memory deficits are evident in early stages of AD. Transgenic mouse models of AD, such as the triple transgenic mice (3xTg) that progressively develop both amyloid and tangle neuropathology, are useful for elucidating factors that might affect the cognitive phenotype from incipient AD. Here we characterize the onset of learning and memory deficits at the age of 5 months in 3xTg mice, by using a Novel Object Recognition task (NOR). Concomitantly, we studied different molecular pathways in hippocampus (HIP) and prefrontal cortex (PFC) in order to establish potential early markers that likely correlate with the memory impairment observed. We found elevated ERK1/2 activity in PFC from 3xTg mice both extra-nuclear at 3 months and nuclear at 6 months of age. Taken together, our results suggest that ERK/MAPK pathway is early deregulated and would be partially responsible for the mild cognitive impairment observed in early stages of AD.