Nav: Home

UCLA cell study reveals how head injuries lead to serious brain diseases

November 16, 2018

UCLA biologists have discovered how head injuries adversely affect individual cells and genes that can lead to serious brain disorders. The life scientists provide the first cell "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 proposes gene candidates for treating brain diseases associated with traumatic brain injury, such as Alzheimer's disease and post-traumatic stress disorder.

The researchers studied more than 6,000 cells in 15 hippocampal cell types -- the first study of individual cell types subject to brain trauma. Each cell has the same DNA, but which genes are activated varies among different cell types. Among the 15 cell types are two that were previously unknown, each with a unique set of active genes.

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

The biologists found that hundreds of genes are adversely affected by mild traumatic brain injury, such as a concussion. These altered genes can later lead to Alzheimer's, Parkinson's and other diseases.

The researchers reproduced a concussion-like brain injury in mice, and studied other mice that did not receive a brain injury. The researchers analyzed thousands of cells in the hippocampus of both groups of mice. Among their findings:
  • The mice without an injury 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. Brain trauma increased the level of Ttr in essentially all of the cell types, the researchers found. They concluded Ttr is important to brain health and may function to bring more thyroid hormone to the brain to maintain metabolism. A thyroid hormone called T4 was injected in mice. T4 improved traumatic brain injury-induced learning deficits and reversed changes in 93 genes that affect learning and memory. This reversal in damage caused by traumatic brain injury is a major new finding. After brain injury, metabolism is substantially reduced. The biologists think T4 may "reboot" metabolism.
  • Researchers found evidence that at least 12 of 15 cell types are negatively affected by brain trauma, some more strongly than others.
  • The researchers were able to see how genes that have been linked to Alzheimer's disease acted within different cell types, providing new details about where these genes act when they are affected by brain trauma. "We are learning which cell types we may want to target in future research," said Xia Yang, a senior author of the study and a UCLA associate professor of integrative biology and physiology. "Maybe Alzheimer's disease-related genes do not have to be active in all different cell types."
  • For the first time, the biologists found several genes that are 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.
  • 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 target for treating this kind of epilepsy.
  • Traumatic brain injury causes changes in how cells communicate with one another (see attached image).
"Knowing which genes in which cells are changing in a particular person can lead to the right treatment for that person," said Yang, who is a member of UCLA's Institute for Quantitative and Computational Biology.

Gomez-Pinilla, who also is a member of UCLA's Brain Injury Research Center, describes the new research as an advance in precision medicine, which holds the promise of individualized treatments for diseases.
-end-
Co-authors of the study are Douglas Arneson, lead author and a graduate student in Yang's laboratory; Guanglin Zhang, Zhe Ying and Yumei Zhuang, who are research scientists in Gomez-Pinilla's laboratory; Hyae Ran Byun, a former postdoctoral scholar in Gomez-Pinilla's laboratory; and In Sook Ahn, a research scientist in Yang's laboratory.

Yang and Gomez-Pinilla's research is funded by the National Institutes of Health. Arneson's research is funded by a Hyde Fellowship and the National Cancer Institute.

University of California - Los Angeles

Related Traumatic Brain Injury Articles:

New test may quickly identify mild traumatic brain injury with underlying brain damage
A new test using peripheral vision reaction time could lead to earlier diagnosis and more effective treatment of mild traumatic brain injury, often referred to as a concussion.
Studies uncover long-term effects of traumatic brain injury
Doctors are beginning to get answers to the question that every parent whose child has had a traumatic brain injury wants to know: What will my child be like 10 years from now?
People with traumatic brain injury approximately 2.5 times more likely to be incarcerated
People who have suffered a traumatic brain injury are approximately 2.5 times more likely to be incarcerated in a federal correctional facility in Canada than people who have not, a new study has found.
Traumatic brain injury associated with long-term psychosocial outcomes
Traumatic brain injury (TBI) during youth is associated with elevated risks of impaired adult functioning, according to a longitudinal study published in PLOS Medicine.
Curbing the life-long effects of traumatic brain injury
A fall down the stairs, a car crash, a sports injury or an explosive blast can all cause traumatic brain injury (TBI).
Is traumatic brain injury associated with late-life neurodegenerative conditions?
Traumatic brain injury (TBI) with loss of consciousness was not associated with late-life mild cognitive impairment, Alzheimer disease or dementia but it appeared to be associated with increased risk for other neurodegenerative and neuropathologic findings, according to a new article published online by JAMA Neurology.
Link found between traumatic brain injury and Parkinson's, but not Alzheimer's
Traumatic brain injury (TBI) with a loss of consciousness (LOC) may be associated with later development of Parkinson's disease but not Alzheimer's disease or incident dementia.
Novel peptide protects cognitive function after mild traumatic brain injury
Scientists at the Hebrew University of Jerusalem have shown that a single dose of a new molecule can protect the brain from inflammation and cognitive impairments following mild traumatic brain injury.
Allen Institute releases powerful new data on the aging brain and traumatic brain injury
The Allen Institute for Brain Science has announced major updates to its online resources available at brain-map.org, including a new resource on Aging, Dementia and Traumatic Brain Injury in collaboration with UW Medicine researchers at the University of Washington, and Group Health.
Developing tools to screen traumatic brain injury therapies
University of Houston biologist Amy Sater will be developing a model for studying traumatic brain injury, thanks to a two-year, $386,000 grant from the Robert J.

Related Traumatic Brain Injury Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Setbacks
Failure can feel lonely and final. But can we learn from failure, even reframe it, to feel more like a temporary setback? This hour, TED speakers on changing a crushing defeat into a stepping stone. Guests include entrepreneur Leticia Gasca, psychology professor Alison Ledgerwood, astronomer Phil Plait, former professional athlete Charly Haversat, and UPS training manager Jon Bowers.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".