Temporal assessment of behavioural alterations and sex influence in an NMDA receptor knockout model of schizophrenia.

PRETELL ANNAN, CA; PAFUNDO DE; BELFORTE, JE

virtual

Congreso; XXXVI Reunión Anual SAN; 2021

Sociedad Argentina de Investigación en neurociencias

Schizophrenia (SZ) is a chronic mental disorder frequently emerging between adolescence andadulthood and encompassing various symptomatic domains. It affects both males and femalesbut clinical differences have been observed. Although the etiology of SZ is still misunderstood,alterations of GABAergic interneurons (INs) are considered to be pathophysiologically relevantsince alterations in cortical INs expressing parvalbumin (PVs) have been found in patients.Normal wiring of cortical circuits relies on the proper postnatal maturation of PVs; thus,alterations of these could be related to the neurodevelopmental aspect of SZ.We have shown that ablation of NMDA receptors (NMDAR) in cortical GABAergic INs frommice at early postnatal age results in SZ-like phenotypes that emerge during adulthood.However, their precise trajectory had not been fully described and sex differences were notassessed. Here, we characterized the time course of behavioral phenotypes (P25-150),evaluating sex differences and presymptomatic stages. As expected, behavioral phenotypes inmale KO mice emerged once adolescence was completed, but female KO mice displayed amore complex trajectory, with transient impairments in Y-maze spontaneous alternationbefore adolescence and abnormal marble burying responses around the transition fromadolescence to adulthood. Thus, while the majority of SZ-related phenotypes emerge inadulthood, specific traits may be present at early stages in a sex-specific manner.