Traumatic injuries, common in athletes and military personnel, quadruple the risk of developing dementia and increase the chances of developing neurodegenerative diseases such as THE A. Furthermore, doctors often have little success in treating it.
A new study published this Thursday in the journal Cell Stem Cell and led by the University of Southern California (USC) has discovered that a protein (TDP-43) drives nerve damage just after injury, a finding that could help as a biological marker to detect traumatic brain injuries and to help control the damage one day.
Brain injuries or trauma cause damage to nerve cells. In more acute phases, patients may have difficulty concentrating and extreme sensitivity to light and noise.
“In the long term, there is a strong correlation between traumatic brain injury and neurodegenerative diseases, which can ultimately be fatal,” explains Justin Ichida, associate professor of Stem Cell Biology and Regenerative Medicine at the John Douglas French Alzheimer’s Foundation at USC and senior author of the work.
Study in organoids
To do the research, the team grew organoids, small groups of human neuronal cells the size of a pinhead that behave like a brain and allow them to be studied.
To simulate what happens at the moment of impact, they hit the organoids with high-intensity ultrasonic waves, thus mimicking severe traumatic brain injuries.
They found that the injured organoids had some characteristics seen in patients with head injuries, such as nerve cell death and pathological changes in two proteins, tau and TDP-43.
The researchers observed that TDP-43, which edits the genetic script that carries the instructions for protein-producing DNA, goes astray in injured organoids and causes nerve death.
That is, in healthy cells – the authors point out – this protein usually resides in the nucleus (where the genetic material is) but after an injury, the protein leaves the nucleus and stops fulfilling its function.
Genetics increase risk
The study also showed that neurons in the cerebral cortex are especially vulnerable to trauma and that genetics can influence the evolution of the disorder.
In fact, organoids derived from patients with genetic risk for neurodegenerative diseases responded to injury more strongly with weaker TDP-43 than healthy ones, a finding that could help explain why some individuals are at greater risk of developing these diseases. diseases after trauma.
“We analyzed all the genes in the human genome to see if we could rescue this lesion by deleting an individual gene”explains Ichida, and thus we found the KCNJ2 gene, which encodes the mechanosensory channel protein on the cell surface.
“If we deleted the gene, all the problems associated with the injury were reversed and the nerve cells were kept alive,” Ichida details.
Inhibition of this gene had a protective effect in organoids derived from patients with and without ALS. The team observed similar effects in mouse models of traumatic brain injury.
The use of KCNJ2 protein blockers before injury not only reduced nerve death, but also the accumulation of TDP-43 in cells, results that suggest that dampening KCNJ2 activity could protect the brain from trauma, he emphasizes. the study.
The team believes these findings will help improve the prevention, diagnosis and treatment of brain injuries, as they could help inform people of their genetic risks and guide safety measures.
Additionally, TDP-43 could also serve as a biomarker to detect traumatic brain injuries and monitor damage one day.
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Source: Gestion
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