Master genes trigger cascade of damage to other genes after brain trauma
It wasn't that long ago that sportspeople were expected to simply shake off blows to the head and keep on playing, but evidence continues to mount regarding the seriousness and potential long-term risks of such injuries. Researchers from the University of California, Los Angeles (UCLA) have now identified a series of master genes that, when damaged through traumatic brain injury, can adversely trigger changes in other genes related to the onset of many neurological and psychiatric disorders.
In a new study published in EBioMedicine, the researchers produced a concussion-like brain injury in a group of rats and then analyzed how their genes had changed as a result. They drew RNA from two separate sources in the rats, the hippocampus and leukocytes, which are white blood cells important in immune system response.
The researchers found a core group of 268 genes in the hippocampus had been altered through the brain injury and a further core group of 1,215 genes in the leukocytes had changed.
While the genetic changes in the hippocampus were not surprising to the researchers, the scale of alterations to the genes in the white blood cells was unexpected. This result suggests the possibility of developing a gene-based blood test that could not only determine whether a brain injury has occurred, but also help predict the likelihood of that injury leading a person to develop Alzheimer's or other disorders in the future.
We have seen several attempts in recent years to develop a blood test that can identify if a concussion or traumatic brain injury has occurred. Most recently, a team at Orlando Health devised a process that can track the biomarker of a protein released into the bloodstream after a brain injury. This new UCLA research excitingly offers the prospect of a more accurate blood test that enables doctors to better understand both the severity of an injury and its potential to have longer term neurological repercussions.
The most compelling result of the study was the identification of over 100 altered genes in the rats that have direct counterparts in humans and are linked to many neurological and psychiatric disorders. As well as several damaged genes in the rats having analogs in humans that have been linked to a predisposition for Alzheimer's, they also found affected genes similar to ones found in humans that are linked to PTSD.
"We believe these master genes are responsible for traumatic brain injury adversely triggering changes in many other genes," said Xai Yang, a senior author of the study. The hope is that in identifying these master genes new drugs could be developed that offer targeted treatments for a variety of brain disorders.
A previous study by the researchers identified several of these master genes, that once altered can cause a cascade effect changing hundreds of other genes. One gene in particular previously identified as a master gene, Fmod, was again noted in this new research as acting to trigger changes in numerous other genes.
The next step for the researchers is to specifically determine how modifications of these master genes can trigger changes in large numbers of other genes. They will also look to identify these particular genetic changes in human subjects by studying people who have suffered traumatic brain injury.
The team's study appears in the journal EBioMedicine