WHICH COGNITIVE DEFICITS CHARACTERIZE THE ALZHEIMER?S DISEASE RAT MODEL MCGILL-RTHY1-APP?

FILIPPIN, FEDERICO; AGUIRRE ALEJANDRA; GONZALEZ GARELLO, TOMAS; JERUSALINSKY, DIANA ALICIA; KORNISIUK, EDGAR; LAVAISE, SERGIO NICOLAS; CUELLO, CLAUDIO; CERCATO, MAGALI CECILIA; BAEZ M. VERÓNICA; BURSTEIN, NICOLE

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA

Alzheimer?s disease (AD) is the major neurodegerative disorder that affect aging people around the world. This disease is characterized by amyloid plaques and hiperphosphorilated Tau tangles that was observed postmortem in AD patients. Several hypothesis were proposed to explain AD etiology; the most relevant is the over production first intracellular and then extracellular of Ab peptide. Over expression of Ab produce aggregation in oligomers (ABOs), first soluble and later insoluble that finally forms fibrils that aggregate in amyloid plaques. ABOs would be toxic for synapses. ABOS binding to several postsynaptic receptors cause oxidative stress in neurons and activates several cascades that ends in neuronal death. Also, circulating ABOs increase inflammation increasing the presence of reactive glia. These mechanisms would explain memory deficits observed in AD. In this work we characterized memory deficit in McGill Thy1 rats (Tg). This rats express the human APP with three of the most common mutation that produce Ab overexpression. One year old hemizygous Tg rats have increased AB intracellular levels which was demonstrated by IHQ. Using these rats, we have characterized cognitive features of hemizygous TGs in parallel with their wild type littermates (WT) to discriminate putative age deficits from those due to amyloidosis. 13 month old TG and WT rats were evaluated in open field (OF), step-through inhibitory avoidance (IA), object location (OL) and object recognition (OR) tasks. These last task were evaluated both for short-term and for long-term memories (STM and LTM).There were no differences between WT and TG rats in OF exploration parameters, showing LT habituation to the environment. TGs seemed to be unable to learn the IA taskin contrast to WT littermates. Neither WTs nor TGs seemed to discriminate OL at variance with younger animals. In contrast, WTs have STM and LTM for OR, while TGs only showed STM for OR.Hence, this TG rat would be an appropriate model for investigating early steps of AD and for evaluating potential therapies to repair cognitive dysfunctions in this sort of pathologies