UCLA biologists have discovered how head injuries negatively affect individual cells and genes that can cause serious brain disorders. Life scientists provide the first "atlas" of the hippocampus, the part of the brain that helps regulate learning and memory when it is affected by traumatic brain injuries. The team also proposes genetic candidates for the treatment of brain diseases associated with traumatic brain injuries, such as Alzheimer's disease and post-traumatic stress disorder.
The researchers studied more than 6,000 cells in 15 types of hippocampal cells: the first study of individual cell types subjected to brain traumas. Each cell has the same DNA, but that the genes are activated varies between different types of cells. Among the 15 types of cells there are two previously unknown, each with a unique set of active genes.
"Each type of cell is different," said Fernando Gomez-Pinilla, a professor of neurosurgery and biology and integrating physiology at UCLA and co-author of the study, which was published in the journal Natural communications.
Biologists have found that hundreds of genes are negatively affected by mild traumatic brain injuries, such as a stroke. These altered genes can lead to Alzheimer's, Parkinson's and other diseases.
The researchers reproduced a brain injury such as concussion in mice and studied other mice that did not receive brain injury. The researchers analyzed thousands of cells in the hippocampus of both age groups. Among his findings:
- Mice without an injury had very low levels in 14 of the 15 types of cells of a gene called Ttr that regulates metabolism, controls thyroid hormones and performs other functions. Cerebral trauma increased the level of Ttr in all cell types, the researchers found. They concluded that Ttr is important for brain health and can work to bring more thyroid hormone to the brain to maintain metabolism. A thyroid hormone called T4 was injected into mice. T4 improved the learning deficits caused by traumatic brain injuries and changed the changes in 93 genes that affect learning and memory. This reversal of the damage caused by traumatic brain injuries is a new discovery. After brain injury, the metabolism substantially reduces. Biologists think that T4 can "restart" metabolism.
- The researchers found evidence that at least 12 of 15 cell types are negatively affected by brain trauma, stronger than others.
- The researchers were able to see how genes that were linked to Alzheimer's disease acted in different types of cells, providing new details on where these genes work when they are affected by a brain trauma. "We are learning what kind of cells we may want to invest in future research," said Xia Yang, lead author of the study and associate professor of biology and integrating physiology at UCLA. "Maybe the genes related to Alzheimer's disease do not have to be active in all types of different cells."
- For the first time, biologists have found several genes that are affected by traumatic brain injuries, which have recently been linked to neurotic behavior in humans. Traumatic brain injury was associated with depression, anxiety, and schizophrenia. This investigation can lead to new treatments for these conditions.
- The injury to the brain can lead to what is known as post-traumatic epilepsy. The researchers found a gene that could serve as a potential goal to treat this type of epilepsy.
- Traumatic brain injury causes changes in the way cells communicate with each other (see attached image).
"Knowing which genes in which cells are changing in a particular person can lead to the proper treatment for that person," said Yang, who is a member of the UCLA Institute for Quantitative and Computational Biology.
Gomez-Pinilla, who is also a member of the UCLA Brain Injury Research Center, describes the new research as an advancement in precision medicine, which has the promise of individualized treatment for illnesses.
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