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Early-age stress ’causes more change to brain than TBI’

Study reveals stress changes activation levels of more genes in the brain than through a bump to the head



Early life stress causes more change to genes in the brain than a head injury, new research has suggested. 

In an animal study, stress was found to change the activation levels of many more genes in the brain than were changed by a bump to the head. 

Experiments in rats suggests the potential of early life stress to lead to a lifetime of health consequences may not be fully appreciated, the research team from Ohio State University said. 

“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,” said senior author Kathryn Lenz. 

“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.”

For the study, 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, a time when rats are developmentally equivalent to a toddler, stressed and non-stressed rats were given either a concussion-like head injury under anaesthesia or no head injury. 

Three conditions – stress alone, head injury alone and stress combined with head injury – were compared to uninjured, non-stressed rats.

The gene expression changes in the hippocampal region of the animals’ brains were examined later in the juvenile period using single-nuclei RNA sequencing.

Stress alone and stress combined with traumatic brain injury (TBI) 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 kinds of changes and mostly to promote flexibility, but sometimes, when the changes are maladaptive, resulting in negative outcomes.

“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,” said first author Michaela Breach.

Both conditions also had an effect on signalling related to oxytocin, a hormone linked to maternal behaviour 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 behaviour, but we’re finding these differing effects with the oxytocin signalling,” Breach said. 

“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.”

In behaviour tests in rats that had aged into adulthood, only animals that experienced early-life stress were prone to more frequently entering a wide-open space – a location that typically makes rodents 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 characterised by risk-taking behaviour or substance use disorders,” Breach said.

The behaviour data pointing to detrimental effects of early-life stress provides further evidence of the need to address adverse childhood experiences, Lenz said.

“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-emphasised how damaging early-life stressors can be if they’re not dealt with.”