Scientist Explores How to 'Unclick' PTSD in the Brain

A traumatic event can alter molecular "switches" placed on the DNA of brain cells. What changes does post-traumatic stress disorder (PTSD) cause in individual cells and whether they can be reversed? Dr. Mykhailo Batiuk, a European Research Council (ERC) grant recipient, investigates.

A deadly threat, an accident, or witnessing a tragic event – ​​some traumatic experiences exceed our coping abilities and can permanently reprogram the brain, causing post-traumatic stress disorder.

"Currently, the most effective form of therapy is psychotherapy combined with antidepressants, but the effectiveness is still low. The problem stems from the fact that we don't fully understand what exactly changes in the brains of PTSD patients. That's why we don't have a fully effective drug," Dr. Batiuk told PAP.

Stress activates the body's hypothalamic-pituitary-adrenal axis, leading to the release of large amounts of stress hormones, including corticosteroids. This systemic response also reaches the brain. PTSD is known to be associated with increased levels of inflammation in the brain, with glial cells—astrocytes and microglia—playing a key role.

Previous research, including those using functional magnetic resonance imaging (fMRI), also reveals which parts of the brain are affected. "The problem primarily affects the prefrontal cortex. This is the part of the brain responsible for cognitive functions and memory, crucial for our normal functioning," explains Dr. Mykhailo Batiuk.

Until now, however, little was known about what these changes look like at the level of individual neurons and other brain cells. The ERC grant recipient aims to fill this knowledge gap.

Dr. Batiuk aims to understand the epigenetic mechanisms involved in PTSD. "You can think of it as a layer of molecular 'switches' superimposed on our DNA. Trauma doesn't change the genetic code itself, but turns these switches on and off. This, in turn, changes the functioning of brain cells and leads to the symptoms of PTSD," explains the researcher.

In his research, the scientist plans to use cutting-edge single-cell genomics tools. This precise approach will allow him to identify which types of brain cells are most affected by trauma and which specific epigenetic "switches" are altered. Identifying these could pave the way for the design of new, targeted drugs that "reset" these switches.

Previous attempts to understand PTSD have relied primarily on studying larger sections of brain tissue ("in bulk"). These studies involved averaging signals from millions of cells, thus losing information about changes in individual cell types.

"The techniques we use allow us to unravel these changes at the single-cell level. One of them is snm3C-seq, or multi-omics sequencing, which allows us to simultaneously study DNA methylation and the spatial organization of chromosomes in a single cell nucleus. When I sequence a single cell, I can see where methylation occurs and which chromosome fragments interact," the scientist announces.

Dr. Batiuk has previously used similar methods to study the mechanisms of schizophrenia and fear memory. Now he wants to combine knowledge from both projects to deeply investigate the cellular basis of PTSD .

The samples for the study come from tissue banks, primarily from the United States, where the culture of organ donation for research is more widespread than in Europe, says Dr. Batiuk. The brain cannot be used for transplantation, making it a valuable research material.

The PAP source expects to gain access to approximately 100 samples. "We'll start with small fragments of the prefrontal cortex, from which we can obtain as many as 50,000-100,000 cells. This is sufficient to conduct advanced analyses," the researcher says.

"We know that DNA methylation is involved in gene silencing, among other things. By comparing a given cell type in PTSD patients with cells from healthy individuals, I will be able to see if and where changes have occurred in the genome. This will allow me to estimate which genes are involved in the development of PTSD. We can then target these genes or regions of the genome using epigenome-modifying tools," he explains.

Research will also be conducted on an animal model – mice.

When asked why he chose the Polish Centre for Technology Development (PORT) in Wrocław to implement the ERC grant, Dr. Batiuk emphasizes the unique nature of the institute. "PORT not only conducts basic research but also focuses on translating its results into clinical practice. I was attracted by the prospect of being able to try to implement the results in collaboration with industry, found a startup, or introduce them into the clinic. Of course, it's too early to talk about this yet. First, we need to find solid therapeutic targets, but in the future, in collaboration with the institute, we will strive to implement them," he concludes.

A total of €761 million was awarded in the ERC (European Research Council) competition, which concluded on September 4th. 478 young researchers received these grants, with the largest number of grants going to scientists from Germany (99), the United Kingdom (60), the Netherlands (44), and France (41). Six researchers working on projects in Poland were also among the winners.

Ludwik Tomal (PAP)

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