Learning and memory is differentially affected in middle aged wild type and McGill-R-Thy1-APP rats according to sex

HABIF M; DO CARMO S; CERCATO M; COLETTIS N; SISTER C; CUELLO C; FILIPPIN F; BERKOWICZ V; JERUSALINSKY D

Congreso; Society for Neuroscience "Global Connectome" Virtual Meeting.; 2021

Society for Neuroscience

Recent studies have shown a sex difference in neuropathology and cognition in mouse models of Alzheimer?s disease (AD). In this study, we investigated the influence of sex on short-term (STM) and long-term memory (LTM) in middle-aged McGill-R-Thy1-APP transgenic (Tg) rats, a model of AD-like brain amyloidosis. In heterozygous (+/-) McGill Tg rats the amyloid pathology is mainly intraneuronal with extracellular plaques developing at advanced age, offering an opportunity for testing cognitive deficits at preplaque stages. 12-13 month old McGill +/- male and female rats and their wild-type (wt) littermates were left to explore an open field for 5min and tested 24hr later. Horizontal (traveled distance) and vertical (rearings) exploration as well as grooming and time spent in the center of the arena vs periphery, were quantified. Most of the exploratory parameters were significantly lower along a session, as well as in the 2nd vs. the 1st exposure, denoting habituation in the 4 groups, without significant differences between them. Rats were then trained in 2-novel object recognition (NOR) and location (NOL) tasks. Both wt and Tg rats discriminated well a new vs. a familiar object 1hr later (short-term memory, STM). However, 24h later (long-term memory, LTM), Tg rats either female or male, did not reach the discrimination criteria. In the NOL task, only wt females performed well to discriminate a new location for a familiar object. For inhibitory avoidance, rats were left in an enlighten compartment, receiving a mild foot shock when entering a dark compartment, and latency to enter it was recorded. 24h later test latencies were significantly higher for both wt and Tg females, and for wt males, though not for Tg males. Furthermore, 14 days later only wt females reached the criteria. In conclusion, both 12-13 month-old wt and Tg+/- rats showed sex-dependent impairments in some cognitive functions: wt males and Tg (both female and male) rats exhibited selective LTM and persistence deficits in associative memories involving spatial reference and/or aversive stimulus compared to wt females. This highlights the importance of including sex as a variable when interpreting cognitive behavior data.