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

Helena Ferreira,Joana Gonçalves,Ana Catarina Sousa,Miguel Castelo-Branco,José Sereno,João Martins

doi:10.3390/metabo12010071

Abstract

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.

Highlights

Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting 1 in 59 children [1]
We performed in vivo proton magnetic resonance spectroscopy to analyze the levels of several metabolites in the prefrontal cortex (PFC) and hippocampus, in juvenile male and female mice, using a genetic model of ASD, tuberous sclerosis complex 2 (Tsc2+/ − ) mice
To identify specific neurochemical profiles in male and female Tsc2+/ − mice, we performed in vivo proton magnetic resonance spectroscopy in both hippocampus and PFC

Summary

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting 1 in 59 children [1]. Deficiencies in social interaction are widely reported in ASD patients (e.g., [4,5,6,7,8]), as well as in animal models of the disorder, who present reduced interaction, abnormal social preference, and lack of preference for social novelty (e.g., [9,10,11,12,13,14]). Patients with ASD present stereotyped, ritualized movements and patterns of behavior, and fixated interests, with an abnormal intensity and concentration [2]. These RRB can be assessed in rodents via analysis of persistent, stereotyped activities such as self-grooming or marble burying [15]. Several authors have reported increased levels of self-grooming behavior [12,16,17,18,19,20,21,22,23,24,25,26] and of marble-burying activity [22,23,27,28,29] in syndromic and environmental mouse models of ASD

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Conclusion