Efeitos comportamentais do estresse por separação maternal são sexo-dependentes e distintos na pré-puberdade e no início da vida adulta

Abstract

Complex interactions among the organism, its environment, and its ontogenesis form the foundation for behavioral patterns observed in adulthood. Both everyday behavior and behavioral disorders can result from developmental processes. This perspective aligns with data indicating that most psychiatric disorders emerge before adulthood, with higher incidence of mood, anxiety, and eating disorders, as well as schizophrenia, during adolescence. Notably, early-life stress exposure is a risk factor for the onset of these disorders. During this period, processes such as neurogenesis, synaptogenesis, and synaptic pruning occur more intensely, with synaptic pruning being one of the most relevant means for refining neuronal communication. The hypothesis of this study is that early-life stress interacts with neurodevelopmental processes and leads to different behavioral outcomes in adolescent and adult mice. To test this hypothesis, male and female mice were subjected to maternal separation stress during the first two weeks of life. From postnatal day P28 or P58, all animals underwent a battery of behavioral tests for assessment of motor/exploratory and anxiety-like behaviors. In this study, we observed that during adolescence, male mice exposed to maternal separation exhibit hyperlocomotion in the open field test, along with an increased latency to first explore the dark compartment in the light/dark box; while females lost the preference for social stimuli characteristic to the adolescence. According to the analysis of variance, the “stress exposure” factor was associated with less time in the dark compartment in the light/dark box, fewer entries into the closed arms and center of the elevated plus maze, as well as fewer crossing between regions. Further, the “sex” factor itself was related to a basal behavioral difference in the light/dark box. When the same tests were performed in adult mice, the only remaining alteration was the influence of exposure to stress in the elevated plus maze. In our study, we observed a shift in early-life stress response from adolescence to adulthood, thus emphasizing the relevance of studying different developmental phases, and highlighting the significance of considering experiences that are particular to formative periods when discussing social well-being and health.