Long-term memory impairment is different in male and female transgenic McGill-R-Thy1-APP rats model of Alzheimer ́s disease

FEDERICO FILIPPIN; MAGALI CERCATO; DIANA JERUSALINSKY; MARTIN HABIF; DANIELA SALAS; EDGAR KORNISIUK; CATERINA SISTER; NATALIA COLETTIS; A. CLAUDIO CUELLO

Villa Carlos Paz, Córdoba

Congreso; XXXIV Reunión Anual SAN 2019; 2019

Sociedad Argentina de Investigacion en Neurociencias

Memory impairment in early Alzheimer Disease (AD) would rely on an increase in soluble Aβ-oligomers, potent neurotoxins altering synaptic plasticity. McGill-R-Thy1-APP Wistar-transgenic (Tg) rats bearing human Amyloid Precursor Protein gene with Swedish and Indiana mutations of familial AD offer an opportunity for testing sex differences in cognitive deficits at AD onset. Homozygous Tg rat already showed cognition deficits at 3 month and intraneuronally human Aβ accumulation from 1st week. Hemizygous Tg (He) show a more subtle phenotype and do not develop extracellular plaques even at 20 months. 12-13 month old (mo) He male (m) and female (f) rats and their wild type litter-mates (WT) were left to explore an open field (OF) for 5min and tested 24hr later; bi-dimen-sional exploration was quantified, being significantly lower in test than in training, denoting habituation. Same rats were trained in a 2-object recognition (OR). WT and Hef, and WTm, discriminated new vs known object 1hr (short-term memory, STM), and 24h (long-term memory, LTM) later, while Hem rats did not.Rats were trained in an inhibitory avoidance step-through (IA), where latencies to avoid a mild footshock were recorded. 24h later/ Test latencies were significantly higher for WT and Hef. and WTm, while there was not significant difference for Hem rats.Hence, 12-13 mo He Tg male rats, though not females, suffer selective STM/LTM deficits, in associative memories with spatial and/or aversive components.