Head injuries can harm and alter hundreds of genes in the brain, increasing risks for a number of psychiatric and neurological disorders.
In a study published in the journal EBioMedicine, researchers reported identifying for the first time a set of master genes believed to control hundreds of other genes that are linked to schizophrenia, depression, autism, attention deficit hyperactivity disorder, stroke, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, and others.
With master genes known, scientists could move to develop new targets for drug treatments for brain diseases. Damaged genes may be even re-modified in the future to reduce chances of disease development.
According to the researchers, genes feature the potential to turn into any kind of protein, and traumatic brain injury can damage the master genes, which leads to alterations in other connected genes.
Senior author Xia Yang said alterations to genes can happen in two ways: first, injury ultimately leads to genes producing irregularly formed proteins, and second, injury can lead to a change in the number of expressed copies a gene has in every cell. Either way, a gene ceases to work as it should.
"Very little is known about how people with brain trauma ... develop neurological disorders later in life. We hope to learn much more about how this occurs," said Fernando Gomez-Pinilla, senior co-author for the study.
Brain Injury And Gene Changes
For the study, the researchers used 20 rats and taught them to escape a maze. Half of the rat subjects were then administered a fluid that mimics concussion-like brain injuries. When all of the rats went through the maze again, those with brain injuries took about 25 percent longer to get out compared with the non-injured rat subjects.
When the researchers took five rats from each group, they extracted RNA from white blood cells critical to the immune system and from the hippocampus, the part of the brain responsible for regulating memory and learning.
Based on their findings, the researchers saw that rats with brain injuries had 1,215 genes altered in the white blood cells while 268 were altered in the hippocampus. They were expecting changes in the brain so they were more surprised observing that major gene changes also occurred in the white blood cells.
Possible Applications
The blood and the hippocampus share almost two dozen altered genes, opening the possibility for gene-based blood tests to identify whether or not a brain injury occurred. At the same time, measuring some of the altered genes could give doctors a hand in predicting who is likely to be at risk of developing Alzheimer's or other brain disorders.
After identifying genes affected by traumatic brain injury and associated with serious diseases, the study may be able to aid in identifying genes that specifically govern inflammation, cell communication, and metabolism, which may also be potential targets for new brain disorder treatments.
Over 100 of the altered genes have human counterparts linked to psychiatric and neurological disorders. For instance, 16 of the rat genes have analogs in humans, which are linked to Alzheimer's predisposition.
The researchers are now looking into the master genes to see if they can be modified and if doing so can change other genes as well.
