UVA explores what causes cell death in the brain

UVA explores what causes cell death in the brain
A recent discovery may help explain conditions such as schizophrenia, depression, bipolar disorder and autism.

CHARLOTTESVILLE, VA (WCAV) - When a person suffers from Alzheimer’s, Parkinson’s and other neurodegenerative diseases, certain brain cells will mysteriously die.

But now research from the University of Virginia School of Medicine may have identified an explanation for those cell deaths.

It suggests the cells die because of a naturally occurring gene variation in brain cells that until recently were assumed to be genetically identical.

It's called “somatic mosaicism” and could explain why neurons in the temporal lobe are the first to die in Alzheimer's and why dopaminergic neurons are the first to die in Parkinson's.

“This has been a big open question in neuroscience, particularly in various neurodegenerative diseases,” said Michael McConnell, PhD, of UVA’s Center for Brain Immunology and Glia. “What is this selective vulnerability? What underlies it? And so now, with our work, the hypotheses moving forward are that it could be that different regions of the brain actually have a different garden of these [variations] in young individuals and that sets up different regions for decline later in life.”

According to a release, the finding emerged unexpectedly from investigations into schizophrenia, and it was in that context that McConnell and his collaborators first discovered the unexpected variation in the genetic makeup of individual brain cells.

The release says the discovery may help explain not just schizophrenia but depression, bipolar disorder, autism and other conditions.

McConnell expects this mosaicism, or a condition that leads to the faulty distribution of genetic material during the mitosis process, would increase with age, meaning that mutations will accumulate over time.

However, working with collaborators at Johns Hopkins, they found the opposite. Younger people have the most mosaicism while older people had the least.

Based on their findings, McConnell says he believes neurons with significant genetic variation may be the most vulnerable to dying, which could explain the idiosyncratic death of specific neurons in different neurodegenerative diseases.

The release says people with the most of such neurons in the temporal lobe might be more likely to develop Alzheimer's.

McConnell says more work needs to be done to fully understand what is happening, since he has only looked at neurons in the frontal cortex of the brain so far.

His studies are also limited by the fact that neurons can be examined only after death, so it can be hard to make direct comparisons.

“Because I'm collaborating with the Lieber Institute and they have this fantastic brain bank, now I can look at individuals' frontal cortex [for the schizophrenia research] and I can look at the temporal lobe in those same individuals,” said McConnell. “So now I can really start to map things out more carefully, building an atlas of different brain regions from many individuals.”

The findings have been published in the scientific journal Cell Reports.

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