Difference in cognitive performance in middle aged female and male McGillThy1App transgenic rats model of Alzheimer disease

MARÍA V. OBERHOLZER; N. COLETTIS; MARTIN HABIF; VANINA GRIPPO; JULIETA RUSSO; RICARDO ALEGRI; CLAUDIO CUELLO; DIANA ALICIA JERUSALINSKY

Mar del PLata

Congreso; Reunion anual de Sociedades de Biociencias; 2022

Sociedad Argentina de Investigacion Clinica

While characterizing learning and memory in heterozygous McGill-R-Thy1-APPtransgenic (Tg) Wistar rat model of Alzheimer disease (AD) with a transgene ofhuman amyloid precursor protein-751 (APP751) with Swedish and Indianamutations of familial AD (Leon et al., 2010), we observed differences betweenfemales and males.Open field: was used to assess spontaneous exploration and habituation to theenvironment. 12 month-old (mo) female and male wt and Tg rats showed similarperformances in the 1st OF session. 24 h later, exploratory parameters weresignificantly lower in Tg and wt rats, indicating that they recognized and habituatedto the environment, consolidating a long-term memory (LTM).Novel object recognition assesses rat’s capacity to discriminate objects. 1h aftertraining with two identical objects (A) and (A’) rats were presented with (A) and anovel (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 (C). Wtrats spent longer exploring (C) than (A), denoting LTM formation, while there werenot significant differences for Tg rats, regardless of sex.24 h later, rats were tested for object location. (A) remained whereas (A’) was movedto a new location. Only wt females denoted spatial discrimination and LTM of theprevious configuration, while wt males and Tg rats did not.Inhibitory avoidance: Each rat was left in a light compartment; when entering a darkone, it gets a mild foot-shock; latency to enter was recorded. 24 h later, latencieswere significantly higher for wt females and males, and Tg females, though not forTg males that did not form/express this associative LTM. 14 days later, latency wassignificantly higher for wt females, though not for wt males nor for Tg rats.Our results showed a sexual dimorphism in associative memory at middle age,emphasizing the relevance of sex while assessing cognitive functions.