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Study reveals how childhood stress changes the brain

A new study conducted by researchers at the University of São Paulo has shed new light on the link between stress experienced during adolescence and the predisposition to mental illness in adulthood. 

The comprehensive research, involving experiments on rats, reveals significant alterations in gene expression within the brain, particularly in genes associated with energy metabolism. 

The study provides valuable insights into how adolescent stress can lead to long-term psychiatric disorders.

Critical time of development 

“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,” explained study first author Thamyris Santos-Silva. 

“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.”

“Adolescence is a critical period for brain plasticity, which is significantly influenced by social experience,” said study co-author Felipe Villela Gomes. “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.”

Prefrontal cortex

The study revolves around the prefrontal cortex, a brain region particularly sensitive to stress during adolescence. This region, crucial for the cognitive control of emotions in adulthood, exhibited reduced gene expression levels associated with mitochondrial respiration in rats subjected to adolescent stress. 

Mitochondria are often referred to as the powerhouses of the cell, and are essential for the chemical energy needed for properly functioning neurons. Ultimately, mitochondria play a critical role in regulating social behavior and stress responses.

Focus of the research 

The research began with an analysis of behavioral responses to stress in late-adolescent rats, including aspects such as anxiety, social interaction, and cognition. The rats were exposed to a stress protocol over ten consecutive days, coinciding with a period of intense brain plasticity. 

Behavioral assessments revealed significant impairments across all tested domains. “We found that stressed animals in this life stage displayed a markedly poor behavioral profile, with anxiety, reduced sociability and impaired cognitive function,” Gomes said.

Changes in gene expression

To further understand these behavioral changes, RNA samples from the rats were sent to the Behavioral Genetics Laboratory of the Brain Mind Institute at the Swiss Federal Institute of Technology in Lausanne, led by Professor Carmen Sandi. 

Through sequencing and bioinformatics analysis, the team identified alterations in the genes of the prefrontal cortex in stressed animals. 

“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,” said Gomes.

Mitochondrial function

The team also found that oxygen consumption by mitochondria in the brains of stressed animals was impaired, underlining the crucial role of mitochondrial function in the observed behavioral profile. 

“We now have evidence of various kinds pointing to the importance of mitochondrial function in this behavioral profile,” said Gomes.

Future research 

Looking ahead, the research team plans to explore whether this behavioral profile can predict an individual’s stress response and its potential to lead to psychiatric disorders. 

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

The study is published in the journal Translational Psychiatry

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