Researchers identify traces of trauma in the young brain and suggest how to erase them

The images of Israeli child hostages freed from Hamas captivity are heartwarming, but for most of these children, this release is only the beginning of a long process of rehabilitation. Countless studies have shown that exposure to war, abuse and other traumatic events at a young age significantly increases the risk of health problems, social problems and mental health problems later in life .

Now, a new study by researchers at the Weizmann Institute of Science gives cause for optimism. In research conducted on mice, published December 1 in Scientists progressa team led by Professor Alon Chen has discovered brain mechanisms that deteriorate following exposure to trauma in early childhood and shown that these changes can be reversible if treated early.

Our brains have a wonderful quality known as plasticity, the ability to change throughout our lives. As might be expected, in our early years, when the brain is still developing, it reaches its maximum plasticity. This manifests itself, for example, in the ability to learn languages, but it also involves an increased sensitivity to traumatic events, likely to leave a scar that only intensifies with age. Many studies provide evidence for the latter effect, but very little is known about how exposure to trauma at a young age affects different types of brain cells and the communication between them in adulthood.

Chen’s lab in Weizmann’s Department of Brain Sciences focuses on the molecular and behavioral aspects of the stress response. In previous studies, Chen’s team examined how stress during pregnancy affects the mice’s 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 understanding of this topic, researchers brought together the strengths of Chen’s lab: his expertise in exploring molecular processes in the brain at the highest possible resolution, using genetic sequencing at the level of single cells; the possibility of using 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 amounts of data generated in this environment, using machine learning and artificial intelligence tools.

This comprehensive behavioral mapping revealed that mice exposed postnatally to a traumatic event – ​​in the case of this study, being neglected by their mothers – displayed a variety of behaviors indicating that they ended up at the bottom of the dominance hierarchy.

“Equivalent behaviors in humans might include high levels of introversion, social anxiety, and an avoidant personality, all known to be characteristic of post-traumatic stress,” says Dr. Juan Pablo Lopez, a former postdoctoral researcher at the Joint Laboratory of Chen to Weizmann and Max Planck. Institute of Psychiatry in Munich and now head of a research group at the Department of Neuroscience at the Karolinska Institute in Stockholm.

In the next stage of the study, the researchers exposed some of the adult mice who had suffered childhood trauma to a stressful social situation: harassment by other mice. Ultimately, they created four groups of adult mice: those that had not been exposed to any trauma; those who were not exposed to childhood trauma but were bullied as adults; mice that were exposed to trauma only during infancy; and mice that were exposed to both childhood trauma and bullying as adults.

To find out how exposure to early trauma disrupts the brain and what results in adulthood, the researchers conducted a careful comparison of the four groups, using RNA sequencing at the single-cell level. of the hippocampus, an area of ​​the brain. known to play an important role in social functioning.

The comparison revealed that early trauma left a mark on different cell types, mainly 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 particularly strong in mice that had been exposed to both childhood trauma and bullying as adults.

Brain cells communicate with each other using electrical signals, which can be excitatory, that is, stimulating or inhibitory. An excitatory signal promotes communication between brain cells, while an inhibitory signal represses it, like the gas and brake pedals of a car. Normal brain function requires a balance between excitatory and inhibitory signals, which is lacking in many psychiatric disorders.

One way to assess the brain’s electrical activity and the balance between excitatory and inhibitory signals is through electrophysiological measurements. Such measurements, carried out in the hippocampus of mice by Dr. Julien Dine, a former scientist at the Weizmann Institute and currently a pharmaceutical electrophysiologist, confirmed the molecular findings: exposure to trauma in early childhood disrupted the balance between excitatory and inhibitory signals in adulthood.

Having discovered a brain mechanism disrupted in adulthood as a result of early trauma – and having identified this disruption as an imbalance between excitatory and inhibitory signals – researchers attempted to find a way to remedy it. During a brief treatment period shortly after the early trauma, they gave the mice a well-known anti-anxiety drug, diazepam, known commercially as Valium, which affects the GABA inhibitory system.

This short treatment led to simply astonishing results: the treated mice were able to completely or almost completely avoid the behavioral future that awaited them and were no longer at the bottom of the social ladder. “Understanding the molecular and functional mechanisms allowed us to neutralize the negative behavioral impact of trauma with a drug administered shortly after exposure to traumatic incidents,” says Kos. “This should certainly not be taken as a recommendation to treat young trauma patients with medication, but our results highlight the importance of early treatment for successful rehabilitation.”

Intense and continuous stress can, at any age, contribute to the development of diseases, ranging from psychiatric disorders to obesity and diabetes. But during the first years of life, as well as in the womb, this stress can have dramatic consequences. “Wars in Israel, Ukraine, Sudan and elsewhere, and the unprecedented global refugee crisis caused, in part, by climate change, as well as a better understanding of the long-term damage caused by exposure to war and violence at a young age. “All of this highlights the need for better rehabilitation capabilities,” says Chen.

“Our new study identifies a key brain mechanism that is particularly sensitive to childhood trauma. But the most exciting part is the prospect of using the plasticity of the young brain to help it recover, thereby avoiding harmful consequences of this trauma in adulthood.”