Adolescent Stress Rewires Brain Energy Genes, Leaving Lasting Marks
Adolescence is a storm of change. The brain rewires itself, hormones surge, and the world feels bigger than ever. But when stress piles on during this window, the effects can echo for years. A new study in rats shows that excessive stress in teen years rearranges gene expression in the brain's command center, particularly the genes that power mitochondria — the tiny engines that keep neurons firing. The research, published in Translational Psychiatry, found that these bioenergy changes persist into adulthood, showing up as anxiety, social withdrawal, and foggy thinking. The work comes from the University of São Paulo's Ribeirão Preto Medical School and was funded by FAPESP.
Adolescence under pressure
Adolescence is a critical period for brain plasticity. The brain of an adolescent rat — and by extension, a human teen — is highly plastic. This plasticity is seen at the molecular level and in behavior. 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. 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.
The prefrontal cortex is a brain region that is extremely susceptible to stress during adolescence. When it matures, it is crucial to enhanced cognitive control of emotions normally observed in adulthood. In rats subjected to stress during adolescence, this region displayed lower levels of expression of genes that play a key role in mitochondrial respiration.
Brain gene changes discovered
Using a rat model, the study showed that stressed adolescent rats exhibited anxiety, reduced sociability, and cognitive impairments linked to changes in genes controlling mitochondrial function in the prefrontal cortex. The researchers exposed rats to a stress protocol for ten consecutive days that coincided with an intense period of brain plasticity. They were then submitted to specific tests to assess their behavior, and the results showed distinct impairment in every case.
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. Consumption of oxygen by mitochondria in the brains of these animals was also found to be impaired by stress.
Mitochondrial dysfunction found
Mitochondria are organelles found in most cells of both humans and rats, as well as many other living organisms. Through cell respiration, they are the main source of chemical energy for the functioning of neurons, one of the main types of brain cells. They therefore help regulate social behavior, including the response to stress.
The study, which was supported by FAPESP, began by analyzing behavioral responses to stress, such as anxiety, social interaction and cognition, in late-adolescent rats. The animals were exposed to a stress protocol for ten consecutive days that coincided with an intense period of brain plasticity. They were then submitted to specific tests to assess their behavior, and the results showed distinct impairment in every case. Mitochondrial respiration (oxygen consumption) was impaired in the brains of stressed rats. Both naïve low-behavioral-z-score and stressed animals exhibited reduced prefrontal phosphorylation capacity and redox dysregulation.
Specific gene alterations identified
Genes encoding subunits of oxidative phosphorylation complexes were significantly down-regulated in stressed animals. The study identified Ndufa10 and Cox6a1 genes as central identifiers for low-behavioral-z-score and stressed animals respectively. Genes encoding subunits of oxidative phosphorylation complexes were significantly down-regulated in both naïve low-behavioral-z-score and stressed animals and positively correlated with behavioral z-score of phenotypes.
Study details and context
The research conducted at University of São Paulo's Ribeirão Preto Medical School (FMRP-USP) was supported by FAPESP and published in Translational Psychiatry. Transcriptomic analysis reveals mitochondrial pathways associated with distinct adolescent behavioral phenotypes and stress response. A distinct pattern of mitochondrial gene expression in the prefrontal cortex (PFC) during adolescence underscores the essential role of mitochondria in brain maturation and the development of mental illnesses.
Behavioral consequences
Stressed animals in this life stage displayed a markedly poor behavioral profile, with anxiety, reduced sociability and impaired cognitive function. The findings underscore the critical impact of adolescent stress on adult brain function and behavior. These findings underscore the critical impact of adolescent stress on adult brain function and behavior — a reality that resonates far beyond the lab.
Original Research
"Transcriptomic analysis reveals mitochondrial pathways associated with distinct adolescent behavioral phenotypes and stress response" by Thamyris Santos-Silva et al., Translational Psychiatry. Open access.
About this stress, genetics, and behavior research news: Author Heloisa Reinert, Source FAPESP, Contact Heloisa Reinert – FAPESP.
Source
https://neurosciencenews.com/teen-stress-genetics-behavior-25539/
