Researchers from the Universidade Estadual Paulista have proven that observed social stress – that witnessed without direct involvement – can impact the brain and behavior differently, depending on biological sex, age and also the intensity and type of stress experienced. The research, carried out with mice, was in the journal Physiology & Behavior.
The work, by the (Fundação de Amparo à Pesquisa do Estado de São Paulo), showed that the effects of stress are more intense when they occur earlier, in younger animals. Surprisingly, in the study, adult females manifest greater resilience compared to males.
“Historically, women have a higher prevalence of anxiety and depression in the world. However, scientific studies have always prioritized men or male animals, which has influenced treatments and our understanding of diseases. It is only more recently that this scenario has begun to change”explains , professor of the Interinstitutional Postgraduate Program in Physiological Sciences, maintained by UFSCar (Federal University of São Carlos) in partnership with Unesp, and one of the authors of the study.
“With this, our study expands the understanding of how stress acts on the brain and behavior and can contribute to the development of more personalized therapeutic approaches, taking into account issues such as the age and biological sex of those affected”says the teacher.
In their work, the researchers sought to mimic common situations of social stress experienced by humans in the laboratory, such as bullyinghumiliation or exposure to trauma by the media. Using tests recognized in animal experimentation, they investigated how this type of stress – whether directly experienced or simply observed – interferes with behavior and brain activity.
“Regions such as the hippocampus and amygdala, responsible for emotional regulation, tend to be especially impacted in these situations, which shows the profound effect of stress on mental health”explains , professor at the Faculty of Pharmaceutical Sciences at Unesp who led the study.
Test protocol
To investigate these effects, researchers used established tests in neuroscience, such as the WSDS (Witness Social Defeat Stress), in which an animal called “witness” observes another animal, the “intruder”, being intimidated by a third animal, the “aggressor”.
All 3 rodents remain inside the same box, but are separated by a transparent barrier. The witness is not attacked, but can see, hear and smell the dispute. The intruder goes through moments of direct confrontation with the aggressor and also remains in a perforated cage within the aggressor’s space, showing signs of submission. This process lasts about 15 minutes and is repeated for 10 days.
After 1 month, the animals undergo another stress session and are then subjected to tests to evaluate responses related to depression. The work also included a control group, in which the animals witnessed peaceful interactions, without aggression.
In addition to including females in the tests, the researchers evaluated both adult mice (60 postnatal days) and young animals (21 postnatal days), which were reevaluated in adulthood.
According to the results, when the younger animals were reassessed a few days later, they showed more robust responses associated with depression. Among adults, males and females reacted differently: some analyzes showed effects only in females, others only in males, indicating behavioral differences.
“In the brain, there were also variations. Females showed less activation in the amygdala and hippocampus, which did not occur in males. In young people, behavioral changes were more intense and affected both sexes, but without brain changes. This means that stress in adulthood revealed more striking sexual differences than in youth”says Daniela Souza.
Because it was originally developed only for males, the researchers needed to adapt the WSDS test protocol for females, who do not exhibit as territorialized behaviors as males, allowing stress to be induced by observation alone.
The adaptation of the protocol showed that adult females, in addition to showing behavioral changes, also demonstrated signs of resilience to stress. “In analyzes related to fear of new objects [um dos impactos medidos depois do estresse]they demonstrated improvement, in addition to less activation in brain areas normally associated with stress. This effect was not observed in males, for example.”says the researcher.
With information from .
