Weizmann Institute researchers unveil new learning about trauma and the young brain
New research exploring the brains of mice has shown how exposure to trauma in infancy alters the brain, and that early treatment to reverse these changes is vital for rehabilitation.
Conducted by the Weizmann Institute, the work shows that although brain mechanisms go awry as a result of exposure to trauma in infancy, these changes may be reversible if treated early, providing “a reason for optimism” amongst advocates for children.
Published recently in Science Advances, a team headed by Professor Alon Chen contributed significantly to the scientific community’s understanding about the way that exposure to trauma at a young age affects the different kinds of brain cells and the communication between them in adulthood.
Brain plasticity is the quality of the brain to change throughout our lives. As may be expected, in our early years, when the brain is still developing, it is at peak plasticity. This manifests in, for example, the aptitude for learning languages, but this also entails a heightened sensitivity to traumatic events, which are liable to leave a scar that only intensifies with age.
Many studies provide evidence for the latter effect, but very little is known about the way that exposure to trauma at a young age affects the different kinds of brain cells and the communication between them in adulthood.
Professor Chen’s laboratory in Weizmann’s Brain Sciences Department focuses on the molecular and behavioral aspects of the response to stress. In previous studies, his team examined how stress during pregnancy affects mouse offspring when they reach maturity.
In the current research, the scientists, led by Dr Aron Kos, studied how trauma experienced shortly after birth affects mouse pups later in life. To advance the understanding of this topic, the researchers pulled together the strengths of Professor Chen’s lab:
- its expertise in exploring the brain’s molecular processes at the highest possible resolution, using genetic sequencing on the level of individual cells;
- the ability to use cameras to track dozens of behavioral variables in a rich social environment intended to recreate natural living conditions; and,
- the ability to process the massive quantities of data generated in this environment, using machine learning and artificial intelligence tools.
This comprehensive behavioural mapping revealed that mice exposed after birth to a traumatic event – in the case of this study, being neglected by their mothers – displayed a variety of behaviors indicating that they found themselves at the bottom of the dominance hierarchy.
“Equivalent behaviors in humans might include high levels of introversion, social anxiety and having an avoidant personality, all known to be characteristic of posttrauma,” explained Dr Juan Pablo Lopez, a former Postdoctoral Fellow in Professor Chen’s joint laboratory.
In the next stage of the study, the researchers exposed some of the adult mice that had experienced trauma in infancy to a stressful social situation: bullying by other mice.
Ultimately, they created four groups of adult mice:
- Those that had not been exposed to any trauma;
- Those that had not been exposed to trauma in infancy but were subjected to bullying as adults;
- Mice that were exposed to trauma only in infancy; and,
- Mice that were exposed to both trauma in infancy and bullying as adults.
To find out how exposure to early trauma disrupts the brain and what happens as a result of this in adulthood, the researchers carried out a meticulous comparison of the four groups, using RNA sequencing at the single-cell level in the hippocampus, a brain area known to play an important role in social functioning.
The comparison revealed that early trauma left a mark on different types of cells, primarily affecting gene expression in two subpopulations of neurons, those belonging to the glutamatergic excitatory system and those belonging to the GABA inhibitory system. This effect was especially strong in mice that had been exposed to both trauma in infancy and bullying as adults.
Having discovered a brain mechanism that is disrupted in adulthood as a result of early trauma – and having identified this disruption as an imbalance between the excitatory and inhibitory signals – the researchers tried to find a way to fix it.
During a brief treatment window shortly after the early trauma, they gave the mice a well-known antianxiety drug – diazepam, known commercially as Valium – which affects the GABA inhibitory system. This short course of treatment led to results that were nothing less than stunning: the treated mice were able to fully or almost fully avoid the behavioral future that awaited them and were no longer at the foot of the social ladder.
“Understanding the molecular and functional mechanisms allowed us to neutralise the negative behavioral impact of trauma with a drug given shortly after exposure to traumatic incidents,” fellow researcher Dr Kos explained.
“This certainly should not be seen as a recommendation to treat young trauma patients with drugs, but our findings do highlight the importance of early treatment for successful rehabilitation.”
To access the findings in full, please see here.
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