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Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction, impaired communication, and repetitive behaviors. ASD presents a 3:1 ratio of diagnosed boys and girls, raising the question regarding sexual dimorphic mechanisms underlying ASD symptoms, and their molecular basis. Here, we performed in vivo proton magnetic resonance spectroscopy in juvenile male and female Tsc2+/− mice (an established genetic animal model of ASD). Moreover, behavior and ultrasonic vocalizations during social and repetitive tasks were analyzed. We found significant sexual dimorphisms in the levels of metabolites in the hippocampus and prefrontal cortex. Further, we observed that female mutant animals had a differential social behavior and presented an increase in repetitive behavior. Importantly, while mutant females displayed a more simplified communication during social tasks, mutant males exhibited a similar less complex vocal repertoire but during repetitive tasks. These results hint toward sex-dependent alterations in molecular and metabolic pathways, which can lead to the sexual dimorphic behaviors and communication observed in social and repetitive environments.

Sex-Dependent Social and Repetitive Behavior and Neurochemical Profile in Mouse Model of Autism Spectrum Disorder