USP researchers identify that stress at this stage causes permanent imbalance in neurons in the prefrontal cortex
A study carried out on rats at the University of São Paulo identified that stressful situations experienced in adolescence tend to cause more profound and lasting changes in the brain than when they occur in adulthood. The research indicated one of the neurological mechanisms behind this difference, offering new clues about the origin of psychiatric disorders such as depression and schizophrenia. The results were in the magazine Cerebral Cortex.
Researchers have proven that exposure to stress in adolescence can interfere with the balance of neurons, compromising the maturation of neural networks and increasing vulnerability to brain dysfunctions that can persist into adulthood.
The research, by Fapesp, demonstrated that stress in adolescence causes permanent changes in the circuits of the prefrontal cortex, the brain region responsible for emotional control and cognitive function.
According to the researchers, trauma at this stage of life disrupts the balance between excitation and inhibition signals in the brain, compromising the functional stability of the organ. In adult rodents, the brain showed greater resilience, with recovery mechanisms that made the effects of stress more temporary.
“Epidemiological studies have already shown that the impact of severe stress is more profound in adolescence. In our work, we have shown that it causes an imbalance in communication between brain cells in both phases of life. However, as the adolescent brain is still in formation, there is not sufficient protection against this impact”explains Felipe Gomes, professor at FMRP (Faculty of Medicine of Ribeirão Preto) at USP and coordinator of the study.
In the research, male rats were subjected to a stress protocol over 10 consecutive days, with foot shocks and movement restrictions. The experiments were carried out in 2 different groups: animals between 31 and 40 days of age (adolescence) and adults (65 to 74 days).
Next, the scientists analyzed, in the 2 groups, short- and long-term changes in the activity of excitatory (glutamatergic pyramidal) and inhibitory (GABAergic interneurons) neurons, both present in the medial prefrontal cortex.
In adolescent rats, stress caused a persistent increase in the activity of excitatory neurons and permanently altered the functioning of inhibitory neurons. The result was a prolonged imbalance, as if the brain was racing, without “a working brake”. It was also observed that, although the strength of inhibitory signals returned to normal, the firing pattern remained irregular, which compromises neural control.
In adults, however, stress caused only a temporary reduction in the activity of inhibitory interneurons, without generating the hyperexcitability observed in adolescents. This allowed the system to rebalance itself after the period of stress.
“The study also showed that the malfunction of interneurons affected the electrical rhythms of the brain. In adolescents, there was a lasting reduction in gamma oscillations, which are fundamental for higher cognitive processes, such as attention and working memory, and which are impaired in schizophrenia. In adults, stress temporarily reduced theta oscillations, which regulate communication between the cortex and other regions, such as the hippocampus. The recovery of this rhythm suggests that brain connectivity has been reestablished”says Gomes.
Neural mechanisms
Previous studies by the same group had already shown that stress in adolescence can induce behaviors similar to those of schizophrenia, while stress in adulthood tends to cause changes more associated with depression.
“Our work advances by revealing the neural mechanisms behind these differences, showing that the moment in life when stress occurs is decisive for the type and duration of changes in the circuits of the prefrontal cortex”, says Flávia Alves Verza, who is investigating the topic in her post-doctorate.
“We were able to deepen this understanding by characterizing the impact of stress at different periods of life on different cell types in the prefrontal cortex, a region frequently affected in psychiatric disorders”adds Gomes.
In addition to sharing exposure to stress as a common risk factor, about 40% of risk genes for schizophrenia are also associated with depression. “In this way, the new study contributed to the hypothesis that a genetically vulnerable individual can develop schizophrenia if exposed to trauma in adolescence, while the same trauma in adulthood can trigger depression. The results reinforce the importance of preventive strategies aimed at young people, especially those in situations of emotional vulnerability”says the researcher.
