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SÃO PAULO, Brazil — Teenagers who are constantly stressed out have a higher risk of suffering mental illness when they enter adulthood. Researchers at the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP) in Brazil have discovered that excessive stress during adolescence can lead to changes in the gene expression in the brain. These changes, particularly in genes related to bioenergy, may impact cell respiration, leading to behavioral issues and psychiatric disorders in adulthood.
Adolescence is known for its profound changes in body and behavior, marked by structural and functional alterations in the brain. These changes are influenced by both neurobiological and social factors.
“Like the human brain, the brain of an adolescent rat is highly plastic. This plasticity is seen at the molecular level and in terms of behavior,” says study first author Thamyris Santos-Silva, who was a doctoral candidate in pharmacology at FMRP-USP at the time of the study, in a media release. “Changes in the expression profiles of specific genes in different brain regions lead to alterations in brain cell connectivity, which spread systemically and can produce persistent alterations in adulthood that correlate with psychiatric disorders.”
Felipe Villela Gomes, a professor in the Department of Pharmacology at FMRP-USP and the article's last author, emphasized the critical nature of adolescence for brain plasticity, shaped significantly by social experiences.
“Susceptibility to adverse social and environmental factors, such as traumas, insults and abuse, increases during this period, and social experience can influence vulnerability and resilience to stress,” explains Gomes.
A key finding of the study is the susceptibility of the prefrontal cortex to stress during adolescence. This brain region is crucial for enhanced cognitive control of emotions in adulthood. In rats exposed to stress during adolescence, there was a decreased expression of genes crucial for mitochondrial respiration in this region.
Mitochondria, the powerhouses of most cells, are essential for cell respiration and are the primary source of energy for neurons. They play a vital role in regulating social behavior and stress response. The study, supported by FAPESP, began by analyzing behavioral responses to stress in late-adolescent rats. The animals underwent a stress protocol for 10 days during a period of intense brain plasticity, showing marked behavioral impairments, including anxiety, reduced sociability, and cognitive dysfunction.
To delve deeper, researchers sent RNA samples to the Behavioral Genetics Laboratory of the Brain Mind Institute at EPFL, led by neuroscience professor Carmen Sandi. Here, scientists sequenced and analyzed messenger RNA using bioinformatics tools, revealing that stress led to alterations in the genes of the prefrontal cortex. Among the most affected genes, several had a link to pathways associated with oxidative stress and mitochondrial function.
The study also found that oxygen consumption by mitochondria in the brains of stressed animals was impaired.
“The analysis showed alterations to the genes of the prefrontal cortex in the stressed animals. Among the ten most affected genes, several were associated with pathways linked to oxidative stress and mitochondrial function, a key cellular component of energy production for the brain,” notes Gomes.
Looking forward, researchers aim to investigate whether this behavioral profile can predict an individual’s response to stress and its potential to lead to psychiatric disorders. They also plan to explore genetic alterations further to understand the links between stress and these changes better, possibly uncovering ways to combat them.
The study is published in the journal Translational Psychiatry.
