Images of Israeli children hostages freed from captivity Hamas or the bereavements to which they have been subjected Palestinian children survived the counteroffensive of Israel They are heartbreaking, but for most of these children, release is just the beginning of a long rehabilitation process. Countless studies have shown that exposure to war, abuse and other traumatic events at a young age significantly increases the risk of disease, social problems and mental health problems later in life.
A new study conducted by researchers from Weizmann Institute of Science provides reason for optimism. In research conducted on mice, a team led by Prof. Alon Chen discovered brain mechanisms that go awry due to exposure to traumatic events in childhood and demonstrated that these changes can be reversible if treated early.
The results of research were published on Science Advances.
Traumatic events: can a young mind be rehabilitated?
Our brain it has a wonderful quality known as plasticity, the ability to change throughout our lives. As you might expect, in our early years, when the brain is still developing, it is at its most plastic.
This manifests itself, for example, in the attitude tolanguage learningbut it also involves a heightened sensitivity to traumatic events, which can leave a scar that only intensifies with age.
Many studies provide evidence for this latter effect, but very little is known about how exposure to traumatic events at a young age influences different types of brain cells and communication with each other in adulthood.
Chen’s laboratory in Weizmann 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 offspring of mice when they reach maturity. In the current research, scientists, led by Dr Aron Kosstudied how trauma experienced immediately after birth affects mouse pups later in life.
To advance understanding of this topic, the researchers brought together the strengths of Chen’s lab: its expertise in exploring the brain’s molecular processes at the highest possible resolution, using the genetic sequencing at the single cell level; 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 enormous amounts of data generated in this environment, using machine learning and artificial intelligence tools.
This comprehensive behavioral mapping revealed that mice exposed postnatally to traumatic events – in the case of this study, being neglected by their mothers – showed a variety of behaviors which indicated that they were at the bottom of the dominance hierarchy.
“Equivalent behaviors in humans could include high levels of introversion, social anxiety And avoidant personalityall known to be characteristic of post-trauma,” says Dr Juan Pablo Lopezformer postdoctoral researcher in Chen’s joint laboratory at Weizmann and Max Planck. Munich Institute of Psychiatry and today head of a research group at the Department of Neuroscience of the Karolinska Institute in Stockholm.
In the next phase of the study, the researchers exposed some of the adult mice who had suffered traumatic events in childhood to a stressful social situation: the bullying 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 trauma in childhood but were subjected to bullying as adults; mice exposed to trauma only during childhood; and mice that were exposed to both trauma in childhood and bullying as adults.
To find out how exposure to early traumatic events disrupts the brain and what happens as a result in adulthood, the researchers carried out a meticulous comparison of the four groups, using cell sequencing.RNA at the single cell levelhippocampusan area of the brain known to play an important role in social functioning.
The comparison revealed that early traumatic events left a mark on different cell types, mainly affecting thegene 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 trauma in childhood and bullying as adults.
Brain cells communicate with each other via electrical signals, which can be excitatory, i.e. stimulating, or inhibitory. An excitatory signal encourages communication between brain cells, while an inhibitory signal represses it, like the accelerator and brake pedals in a car. Normal brain functioning requires a balance between excitatory and inhibitory signals, which is lacking in many psychiatric disorders.
One of the ways to evaluate the electrical activity of the brain and the balance between excitatory and inhibitory signals is through electrophysiological measurements. Such measurements, performed in the hippocampus of mice by Dr. Julien Dine, a former Weizmann Institute scientist and currently a pharmaceutical electrophysiologist, supported the molecular findings: exposure to traumatic events in early life disrupted the balance between excitatory and inhibitory signals in adulthood.
Having discovered a brain mechanism that is disrupted in adulthood due to early traumatic events and having identified this disruption as an imbalance between excitatory and inhibitory signals, the researchers set out to find a way to fix it.
During a short treatment window, immediately after the initial traumagave mice a known anxiolytic drug, diazepam, known commercially as Valium, which affects the GABA inhibitory system.
This short course of treatment led to nothing less than surprising results: the treated mice were able to completely or almost completely avoid the behavioral future that awaited them and no longer found themselves at the bottom of the social ladder. “Understanding the molecular and functional mechanisms has allowed us to neutralize thenegative behavioral impact of trauma with a drug administered shortly after exposure to traumatic incidents,” explains Kos.
“This certainly should not be seen as a recommendation to treat young trauma patients with drugsbut our findings highlight the importance of early treatment for successful rehabilitation.”
The intense and continuous stress can, at any age, contribute to development of diseasescome on psychiatric disorders toobesity et al diabetes. But in the first years of life – and even in the womb – such stress can have dramatic consequences.
.”The wars in Palestine, Ukraine, Sudan and elsewhere, and the unprecedented global crisis of refugees caused, in part, by climate changes, along with a greater 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 capabilities rehabilitation“, says Chen.
“Our new study identifies a key brain mechanism who is particularly sensitive to traumatic childhood events. But the most exciting part is the prospect of using the plasticity of the young brain to help it recover, avoiding the toll that this trauma can take in adulthood.”
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