Disorders of the Nervous System
Author: Mauro Exequiel Carlos Alfaro | Email: exequielalfaro16@gmail.com
Martin Habif1°, Mauro Exequiel Alfaro1°,Natalia Colettis1°2°, Maria Victoria Oberholzer1°3°, Maria Belén González1°, Diana Jerusalinsky1°
1° Instituto de Biología Celular y Neurociencia (IBCN) “Prof. EDUARDO DE ROBERTIS” Facultad de Medicina – Universidad de Buenos Aires & CONICET
2° IQUIFIB – INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS “PROF. ALEJANDRO C. PALADINI”
3° INCYT – INSTITUTO DE NEUROCIENCIA COGNITIVA Y TRASLACIONA
Recent studies highlight sex differences in neuropathology and cognition in Alzheimer’s disease (AD) models. We examined the impact of sex on short-term (STM) and long-term memory (LTM) in middle-aged McGill-R-Thy1-APP transgenic (Tg+/-) rats, an AD-like amyloidosis model. Male and female Tg rats, along with wild-type (wt) littermates, were tested in an open field (OF), to assess bidimensional and vertical (rearings) exploration. Traveled distance revealed no significant differences between sexes or genotypes, though males had fewer rearings than females. In a novel object recognition (NOR) task, both wt and Tg rats displayed STM, but Tg rats failed to meet LTM criteria after 24h. In the novel object location (NOL) task, only wt females performed well to discriminate a new location for a familiar object. In inhibitory avoidance (IA), where rats received a mild shock upon entering a dark compartment, wt females showed higher latencies 24h later, indicating better LTM. After 14 days, only wt females maintained this memory performance. Our study found sex-dependent cognitive impairments, with wt males and Tg rats (both sexes) showing deficits in LTM and associative memories, particularly in tasks involving spatial reference and aversive stimuli. These findings suggest that similar sex differences in cognition may occur in preclinical AD, emphasizing the need for improved early detection methods, as these changes may be masked by neuronal and cognitive reserve in humans.