Difference in cognitive performance in middle aged female and male McGill-R-Thy1-hAPP transgenic rat model of Alzheimer disease

MARTIN HABIF; RICARDO ALEGRI; M. V. OBERHOLZER; ALEJANDRO JOSIOWICZ; CLAUDIO CUELLO; NATALIA CLAUDIA COLETTIS; JULIETA RUSSO; DIANA ALICIA JERUSALINSKY

Buenos Aires

Simposio; Simposio LATBRAIN 2022; 2022

While characterizing learning and memory in heterozygous McGill-R-Thy1-APP transgenic (Tg) Wistar rat model of Alzheimer disease (AD) (Leon et al., 2010), we observed differences between females and males. Open field task (OF) was used to assess spontaneous exploration and habituation to the environment. 12 month-old female and male wt and Tg rats showed similar performances in the first OF session. 24 h later, exploratory parameters were significantly lower in Tg and wt rats, indicating that they recognized and habituated to the environment, consolidating a long-term memory (LTM). Novel object recognition assesses rat?s capacity to discriminate objects. 1h after training with two identical objects (A) and (A?) rats were presented with (A) and a novel object (B). Rats spent significantly longer exploring (B) than (A), expressing a short-term memory (STM). 24h later, they were presented with (A) and a novel object (C). Wt rats spent longer exploring (C) than (A), denoting LTM formation, while there were no significant differences for Tg rats, regardless of sex. 24 h later, rats were tested for object location. (A) remained whereas (A?) was moved to a new location. Only wt females denoted spatial discrimination and LTM of the previous configuration, while wt males and Tg rats did not. Inhibitory avoidance: Each rat was left in a light compartment; when entering a dark one, it gets a mild foot-shock; latency to enter the latter was recorded. 24 h later, latencies were significantly higher for wt females and males, and Tg females, though Tg males did not form/express this associative LTM. 14 days later, latency was significantly higher for wt females, though not for wt males nor for Tg rats.Our results show a sexual dimorphism in associative memory at middle age, emphasizing the relevance of sex while assessing cognitive functions.