Early-life stress alters brain genes more than a head injury

A new study has revealed alarming insights on the impact of early-life stress on brain development. According to the researchers, stress experienced in early life causes more gene expression changes in the brain than a head injury. 

This revelation stems from an animal study aimed at understanding the interplay between childhood stress and brain injury consequences in later life.

Focus of the study 

The study, led by Professor Kathryn Lenz of The Ohio State University, involved an animal model where newborn rats were separated from their mothers to simulate the effects of adverse childhood experiences. 

These experiences, which can range from traumatic events to prolonged stress, are very common. They are known to increase the risk of various mental and physical health issues in adulthood.

Head injuries are also common in young kids, particularly from falling. These injuries can be linked to mood disorders and social problems later in life. 

Brain development

“But we don’t know how those two things can interact,” said Professor Lenz. “We wanted to understand whether experiencing a traumatic brain injury in the context of early life stress circumstances could modulate the response to the brain injury.” 

“And using an animal model allows us to really get into the mechanisms through which these two things might be impacting brain development as it’s occurring.”

How the research was conducted 

For the investigation, the newborn rats were separated from their mothers daily for 14 days. On day 15, at an age equivalent to a human toddler, both stressed and non-stressed rats were given either a concussion-like head injury under anesthesia or no head injury. 

The research team, including first author Michaela Breach, a graduate student in Lenz’s lab, focused on examining gene expression changes in the hippocampal region of the rats’ brains. 

The experts analyzed the gene changes associated with three conditions: stress alone, head injury alone, and the combination of both. 

Critical insights

The experts found a higher number of genes exhibiting differential expression due to early-life stress compared to those affected by traumatic brain injury (TBI).

Both stress alone and stress combined with traumatic brain injury activated pathways in excitatory and inhibitory neurons associated with plasticity, which is the brain’s ability to adapt to changes.

“This may suggest that the brain is being opened up to a new period of vulnerability or is actively changing during this period of time when it could program later life deficits,” Breach said.

Oxytocin signaling 

The researchers found differing effects on oxytocin signaling, a hormone linked to social behavior and bonding, between stress and brain injury scenarios. Stress activated this pathway, while brain injury alone inhibited it.

“Both stress and TBI are linked to abnormal social behavior, but we’re finding these differing effects with the oxytocin signaling,” said Breach. 

“That demonstrates that the effect of stress might modulate how TBI is changing the brain since the combination treatment was different from TBI on its own. Oxytocin is involved in the response to stress and repair, so that may mean it could be an interesting modulator for us to pursue in the future.”

Risky behavior 

Rats exposed to early-life stress showed a tendency for riskier behavior in adulthood, aligning with human data linking early-life stress to conditions characterized by risk-taking behaviors.

Once the rats had aged into adulthood, behavior tests showed that only animals in the early-life stress group were prone to more frequently entering a wide-open space where rats would typically feel vulnerable to predators.

“Overall, that suggests they might be taking more risks later in life, which is consistent with human data showing that early life stress can increase the risk for certain conditions like ADHD, which can be characterized by risk-taking behavior or substance use disorders,” said Breach.

Study implications 

Professor Lenz said the behavior data provides further evidence of the need to address adverse childhood experiences.

“Things like social support and enrichment can buffer the effects of early-life stress – that has been shown in animal models and in people,” she said. “I don’t think it can be over-emphasized how damaging early-life stressors can be if they’re not dealt with.”

This first set of experiments in rats suggests early life stress’s potential to lead to a lifetime of health consequences may not be fully appreciated, noted Professor Lenz.

“We found many, many, many more genes were differentially expressed as a result of our early life stress manipulation than our traumatic brain injury manipulation.”

“Stress is really powerful, and we shouldn’t understate the impact of early life stress on the developing brain. I think it tends to get dismissed – but it’s an incredibly important public health topic.”

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