In animal studies, childhood stress is linked to risk-taking in adults.
A surprising thing happened when researchers began to explore whether childhood stress exacerbates the effects of childhood traumatic brain injury on health and behavior later in life: In one animal study, stress altered the activation level of many more genes in the brain than were changed by a blow to the head.
It is already known that head injuries are common in young children, especially from falls, and can be associated with mood disorders and social difficulties that arise later in life. Adverse childhood experiences are also very common and can increase the risk of illness, mental disorders, and substance misuse in adulthood.
Adverse Childhood Experiences (ACEs)
Adverse Childhood Experiences (ACEs) are potentially traumatic events that occur in childhood. ACEs can include violence, abuse, and growing up in a family with mental health or substance use issues. Toxic stress caused by ACEs can alter brain development and affect how the body responds to stress. ACEs are linked to chronic health problems, mental illness, and substance misuse in adulthood. However, ACEs can be prevented.
Preventing ACEs can help children and adults thrive and potentially:
- Lower risk of diseases such as depression, asthma, cancer and diabetes in adulthood.
- Reduce risky behaviors such as smoking and heavy drinking.
- Improve education and employment potential.
- Prevent ACEs from being passed from one generation to another.
Research Methodology and Results
“But we don’t know how these two things might interact,” said study senior author Kathryn Lenz, associate professor of psychology at Ohio State University. “We wanted to understand whether experiencing a traumatic brain injury in the context of stressful circumstances early in life could modulate the brain injury response. And using an animal model allows us to really get into the mechanisms through which these two things may be impacting brain development as it occurs.”
This first set of experiments in mice suggests that the potential for early stress to lead to lifelong health consequences may not be fully appreciated, Lenz said.
“We found that many, many more genes were differentially expressed as a result of our manipulation of childhood stress than our manipulation of traumatic brain injury,” Lenz said. “Stress is really powerful and we shouldn’t underestimate the impact of early life stress on the developing brain. I think it tends to be dismissed – but it is an extremely important public health issue.”
The research poster was presented on November 12, 2023, at Neuroscience 2023, the annual meeting of the Society for Neuroscience.
The researchers temporarily separated newborn rats from their mothers daily for 14 days to induce stress that mimicked the effects of adverse childhood experiences, which include a variety of potentially traumatic events. On day 15, a time when mice are developmentally equivalent to a small child, both stressed and unstressed mice suffered either a concussion-like head injury under anesthesia or no head injury. Three conditions – stress alone, traumatic brain injury alone, and stress combined with traumatic brain injury – were compared with uninjured, non-stressed rats.
Key Findings and Implications
First author Michaela Breach, a graduate student in Lenz’s lab, examined changes in gene expression in the hippocampus region of the animals’ brains in the late juvenile period using single nuclei.
Stress alone and stress combined with traumatic brain injury (TBI) have produced some noteworthy results. Both conditions activated pathways in excitatory and inhibitory neurons associated with plasticity, which is the brain’s ability to adapt to all types of changes – mostly to promote flexibility, but sometimes when the changes are maladaptive, resulting in negative outcomes .
“This may suggest that the brain is being opened to a new period of vulnerability or is actively changing during this time period that could program deficits later in life,” Breach said.
Both conditions also affected signaling related to oxytocin, a hormone linked to maternal behavior and social bonding. Stress alone and combined with TBI activated this oxytocin pathway, but brain injury alone inhibited it.
“Both stress and TBI are linked to abnormal social behavior, but we are finding these different effects with oxytocin signaling,” Breach said. “This demonstrates that the effect of stress can modulate how TBI is changing the brain, as the combined treatment was different from TBI alone. Oxytocin is involved in the stress response and repair, which could mean it could be an interesting modulator for us to pursue in the future.”
In behavioral tests on rats that reached adulthood, only animals that experienced stress in childhood were likely to enter an open space more often – a place that typically makes rodents feel vulnerable to predators.
“Overall, this suggests that they may be more at risk later in life, which is consistent with human data showing that early-life stress can increase the risk of certain conditions such as
This work was supported by the Chronic Brain Injury Institute of Ohio State, the Brain Injury Association of America, and a National Science Foundation Graduate Research Fellowship.
Poster: PSTR159.22/II6 – Examining the impact of early life stress and pediatric TBI on the developing hippocampal transcriptome and behavioral development in rats.