UCLA biologists discover how head injuries can lead to serious brain disorders

UCLA biologists have discovered how head injuries negatively affect individual cells and genes that can lead to serious brain disorders. Scientists specializing in life provide the first cellular atlas of the hippocampus, the part of the brain that helps regulate learning and memory, when it is affected by traumatic brain injury. The team also offers gene candidates to treat 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 hippocampus cells, the first study of individual cell types prone to brain trauma. Each cell has the same DNA, but the activated genes vary depending on the cell types. Of the 15 cell types, there are two that were previously unknown, each with a unique set of active genes.

"Every cell type is different," said Fernando Gomez-Pinilla, professor of neurosurgery and integrative biology and physiology at UCLA, and co-lead author of the study, published in the journal Nature Communications.

Biologists have discovered that hundreds of genes are negatively affected by mild traumatic brain injury, such as a concussion. These altered genes can eventually lead to Alzheimer's disease, Parkinson's disease and other diseases.

The researchers reproduced a concussion-like brain lesion in mice and studied other mice with no brain injury. The researchers analyzed thousands of cells in the hippocampus of both groups of mice. Among their discoveries:

• Wound-free mice had very low levels in 14 of the 15 cell types of a gene called Ttr that regulates metabolism, controls thyroid hormones and performs other functions. The researchers found that brain trauma increased the level of Ttr in virtually all cell types. They concluded that Ttr is important for brain health and that it can help bring more thyroid hormones to the brain to maintain metabolism. A thyroid hormone called T4 was injected into mice. The T4 has improved learning deficits induced by traumatic brain injury and reversed the modifications of 93 genes that affect learning and memory. This reversal of the damage caused by traumatic brain injury is a major new discovery. After a brain injury, the metabolism is greatly reduced. Biologists think that T4 could "restart" the metabolism.
• The researchers found evidence that at least 12 of the 15 cell types are negatively affected by brain trauma, some more strongly than others.
• The researchers were able to see how genes linked to Alzheimer's disease were acting within different cell types, providing new details about the behavior of these genes when they undergo brain trauma. "We are learning what types of cells we might want to target in our future research," said Xia Yang, lead author of the study and associate professor of Integrative Biology and Physiology at the University of Beijing. ; UCLA. "Maybe genes linked to Alzheimer's disease do not necessarily have to be active in all types of cells."
• For the first time, biologists have discovered several genes affected by traumatic brain injury, which has recently been linked to neurotic behavior in humans. Traumatic brain injury has been associated with depression, anxiety and schizophrenia. This research could lead to new treatments for these conditions.
• A brain injury can lead to what is called post-traumatic epilepsy. The researchers have discovered a gene that could serve as a potential target for treating this type of epilepsy.
• Traumatic brain injury causes changes in how cells communicate with each other (see attached image).

"Knowing which genes cells change in a given person can lead to the proper treatment for that person," said Yang, a member of UCLA's Institute of Quantitative and Computational Biology.

Gomez-Pinilla, who is also a member of the UCLA's Center for Brain Injury Research, describes this new research as a breakthrough in precision medicine, likely to offer individualized treatments for diseases.