SELECTIVE LONG TERM MEMORY IMPAIRMENT IN TRANSGENIC MCGILL-R-THY1-APP RAT MODEL OF ALZHEIMER´S DISEASE

HABIF, MARTIN; FILIPPIN, FEDERICO; SALAS, DANIELA ALEJANDRA; CERCATO, MAGALÍ CECILIA; COLETTIS, NATALIA CLAUDIA; CUELLO, A. CLAUDIO; JERUSALINSKY, DIANA ALICIA

Montreal

Congreso; ISN-ASN Meeting, Montreal, Canada. August 4th-8th, 2019; 2019

ISN-ASN

Memory impairment in early Alzheimer Disease (AD) is hypothesised to rely on the initial increase in soluble Aβ-oligomers, potent neurotoxins altering synaptic plasticity.McGill-R-Thy1-APP Wistar-transgenic (Tg) rats, bearing human Amyloid Pre-cursor Protein with Swedish and Indiana mutations of familial AD, offer a singular opportunity for testing learning and memory abilities at AD onset. Homozygous Tg rats show cognition deficits at 3 months; human Aβ accumulates intra-neu-ronally from first postnatal week and develops extracellular amyloid pathology by 6-9 months. Hemizygous Tg (He) show a more subtle phenotype and do not de-velop extracellular plaques even at 20 months.13 month old He rats and their wild type litter-mates (WT) were left to freely explore an open field (OF) for 5min and tested 24hr later (long-term-memory, LTM); bi-dimensional exploration was quantified, being significantly lower in test than in training for both groups.Rats were then trained in a two object recognition task (OR); both WT and He dis-criminated new vs. known object 1hr later (short-term-memory, STM), while He rats did not show LTM.They were then trained in an inhibitory avoidance (IA) to a mild foot-shock task. Latencies to go from an enlightened to a dark compartment where they get the shock, were recorded. Test latencies 24hr later, were significantly higher than training latencies for WT, while remained unchanged for He.Therefore, unlike WT, He evidenced deficits in memory formation for object dis-crimination and for an associative memory involving aversive and spatial components.