Study helps explain why stress in adolescence may lead to predisposition to mental illness in adulthood

Excessive stress during adolescence can cause alterations in the profile of genes expressed in the brain, particularly those associated with bioenergetic functions. These alterations can affect cellular respiration, leading to behavioral problems and psychiatric disorders in adulthood, according to a study in rats carried out by researchers from the Ribeirão Preto Faculty of Medicine of the University of São Paulo (FMRP- USP) in Brazil.

The results are published in the journal Translational psychiatry.

It’s no secret that many changes occur in our bodies and behavior during adolescence, when the brain undergoes structural and functional alterations shaped by both neurobiological and social factors.

“Like the human brain, the brain of an adolescent rat is very plastic. This plasticity is seen at the molecular level and in terms of behavior. Changes in the expression profiles of specific genes in different regions of the brain lead to alterations in “brain cell connectivity, which spreads systemically and can produce persistent alterations in adulthood that correlate with psychiatric disorders,” said Thamyris Santos-Silva, first author of the article. At the time of the study, she held a Ph.D. candidate in pharmacology at FMRP-USP.

“Adolescence is a critical period for brain plasticity, which is significantly influenced by social experience,” added Felipe Villela Gomes, last author of the article and professor in the Department of Pharmacology at FMRP-USP. “Susceptibility to adverse social and environmental factors, such as trauma, insults, and abuse, increases during this period, and social experience may influence vulnerability and resilience to stress.”

The prefrontal cortex is a region of the brain that is extremely sensitive to stress during adolescence. As he matures, it is crucial to improve the cognitive control of emotions normally observed in adulthood. In rats subjected to stress during adolescence, this region showed lower expression levels of genes playing key roles in mitochondrial respiration.

Mitochondria are organelles found in most cells of humans and rats, as well as in many other living organisms. Through cellular respiration, they provide the main source of chemical energy necessary for the functioning of neurons, one of the main types of brain cells. They therefore help to regulate social behavior, particularly the response to stress.

The study began by analyzing behavioral responses to stress, such as anxiety, social interactions and cognition, in rats in late adolescence. The animals were exposed to a stress protocol for ten consecutive days coinciding with an intense period of brain plasticity. They were then subjected to specific tests to assess their behavior, and the results showed in each case a distinct impairment.

“We found that animals stressed at this stage of life showed a markedly poor behavioral profile, with anxiety, reduced sociability and impaired cognitive function,” Gomes said.

To find out whether these variations were reflected in gene expression, the researchers sent RNA samples to the behavioral genetics laboratory at the Brain Mind Institute (BMI) at the École Polytechnique Fédérale de Lausanne (EPFL). The laboratory is led by Carmen Sandi, professor of neuroscience.

To study gene expression in the rat brains, the laboratory sequenced messenger RNA and analyzed the results using bioinformatics tools.

“The analysis showed alterations in genes in the prefrontal cortex in stressed animals. Among the ten most affected genes, several were associated with pathways related to oxidative stress and mitochondrial function, a key cellular component in the production of “energy for the brain,” Gomes said. said.

Oxygen consumption by mitochondria in the brains of these animals was also found to be altered by stress. “We now have evidence of all kinds highlighting the importance of mitochondrial function in this behavioral profile,” Gomes said.

The next steps for researchers will be to determine whether this behavioral profile can serve as a basis for predicting an individual’s reaction to stress and to what extent this actually leads to the development of psychiatric disorders.

“Another avenue to advance the study would be to focus on genetic alterations, performing tests to find out what happens when gene expression decreases or improves. This could provide more evidence about the links between stress and the alterations in question, and even indicate ways to advance the study. to combat them,” said Gomes.