Isolamento neonatal em ratos induz endofenótipos do transtorno do espectro autista com diferenças entre sexos

Abstract

Autism or Autistic Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction and communication, with restricted and repetitive patterns of behavior, interests, and activities. It has a multifactorial etiology, involving genetic and environmental factors and with global prevalence in constant increase. As environmental factors were strongly related to autism, studies that use insults and environmental risk factors have become critical. Thus, the present study induced, through neonatal isolation, endophenotypes of ASD with gender differences in rodents, focusing on social impairment, main symptoms present in the disorder and fundamental for diagnosis. This is a mixed developmental study conducted in childhood and periadolescence of males and females. Wistar Rattus norvegicus pairs were used for breeding purposes and subsequent use of pups for experimentation. After birth, neonates were randomly divided into 4 groups: control, social isolation, saline social isolation, and Risperidone social isolation. Treatment with saline or Risperidone was orally (o.v). Behavioral tests were social aggregation, open field, prosocial help, empathy / emotional contagion and play behavior. After the tests, part of the animals was perfused for histopathological analysis and part was euthanized to remove brain areas involved in the ASD (frontal cortex, striated body and hippocampus) for biochemical analysis. The results showed that neonatal isolation can induce autism endophenotypes with gender differences, such as the presence of repetitive and stereotyped behaviors, locomotor hyperactivity, anxiety responses in new environments, as well as impaired empathy and reduced frequency of play behaviors. This study showed that neonatal isolation can be used to investigate the influence of environmental factors on the genesis of ASD, in addition to opening the way for further investigations and perspectives for studies of the pathophysiology of autism, as well as new therapeutic strategies.