A surprising thing happened when researchers began exploring whether early-life stress worsened the effects of childhood head trauma on health and behavior later in life: in an animal study , stress changed the activation level of many more genes in the brain than was the case. a bump on the head.
We already know that head injuries are common in young children, particularly due to falls, and can be linked to mood disorders and social difficulties that appear later in life. Adverse childhood experiences are also very common and can increase the risk of illness, mental illness, and substance abuse in adulthood.
“But we don’t know how these two things may interact,” said Kathryn Lenz, lead author of the study and associate professor of psychology at Ohio State University. “We wanted to understand whether experiencing head trauma in the context of stressful circumstances early in life could modulate the response to brain injury. And using an animal model allows us to really understand the mechanisms by Which two things could impact brain development as it occurs.
This first set of experiments in rats suggests that the potential for early-life stress to lead to lifelong health consequences may not be fully appreciated, Lenz said.
“We found that many more genes were differentially expressed as a result of our manipulation of early life 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 brain development. I think it tends to be overlooked, but it is a topic extremely important public health.”
The research poster was presented today (November 12, 2023) at Neuroscience 2023, the annual meeting of the Society for Neuroscience.
Researchers temporarily separated newborn rats from their mothers daily for 14 days to induce stress mimicking the effects of adverse childhood experiences, which include a variety of potentially traumatic events. On day 15, when rats are developmentally equivalent to toddlers, both stressed and non-stressed rats suffered either concussion-like head trauma under anesthesia or no head trauma at all. Three conditions – stress alone, head injury alone, and stress combined with head injury – were compared to uninjured and unstressed rats.
First author Michaela Breach, a graduate student in Lenz’s lab, examined gene expression changes in the hippocampal region of the animals’ brains later in the juvenile period using mononuclear RNA sequencing.
Stress alone and stress combined with traumatic brain injury (TBI) have produced some remarkable results. Both conditions activated pathways in excitatory and inhibitory neurons associated with plasticity, which is the brain’s ability to adapt to all kinds of changes – primarily to promote flexibility, but sometimes, when changes are maladaptive, this which leads to negative results.
“This may suggest that the brain is opening itself to a new period of vulnerability or actively changing during this period where it could be programming deficits later in life,” Breach said.
Both conditions also had an effect on signaling related to oxytocin, a hormone linked to maternal behavior and social bonding. Stress alone and combined with head trauma activated this oxytocin pathway, but brain injury alone inhibited it.
“Stress and head injury are both linked to abnormal social behavior, but we see these different effects with oxytocin signaling,” Breach said. “This demonstrates that the effect of stress could modulate how TBI changes the brain since the combined treatment was different from TBI itself. Oxytocin is involved in the stress response and repair, which could mean that ‘it could be an interesting modulator for us to pursue in the future.
In behavioral tests with adult rats, only animals that experienced stress early in life were inclined to enter a large space more frequently – a place that typically makes rodents vulnerable to predators.
“Overall, this suggests that they may take more risks later in life, consistent with human data showing that stress early in life may increase the risk of certain conditions like ADHD, which may be characterized by risky behavior or substance use disorders,” Breach said.
Behavioral data highlighting the detrimental effects of early-life stress provide further evidence for the need to address adverse childhood experiences, Lenz said.
“Things like social support and enrichment can buffer the effects of stress early in life – this has been shown in animal models and in humans,” she said. “I don’t think it can be overstated how damaging early life stressors can be if left untreated.”
This work was supported by the Chronic Brain Injury Institute at Ohio State, the Brain Injury Association of America, and a National Science Foundation Graduate Research Fellowship.
Other co-authors include Ethan Goodman, Jonathan Packer, Ale Zaleta Lastra, Habib Akouri, Zoe Tapp-Poole, Cole Vonder Haar, Jonathan Godbout and Olga Kokiko-Cochran.
