Anxiety and post-traumatic stress disorder linked to increased gray myelination

Reported by scientists at the University of California, Berkeley and the University of California, San Francisco), offer a possible explanation for why some people are resilient and others vulnerable to traumatic stress, and various symptoms -- avoidant behavior, anxiety and fear, such as -- Caused by such pressure on memory

If, as the researchers suspect, extreme trauma leads to increased myelination, the finding could lead to treatments—drugs or behavioral interventions—to stop or reverse myelination and alleviate the sequelae of extreme trauma

Myelin is a layer of fatty substances and proteins that wraps around neuron axons—essentially, an insulator that wraps around brain wiring—to facilitate the long-distance transmission of signals, which in turn facilitates communication between distant regions of the brain.

But the new study found increased myelination of axons in the so-called "gray matter," where most neurons' cell bodies are located, and where most of the connections are not insulated from myelin

Researchers at the San Francisco Veterans Affairs Medical Center performed brain MRI scans of 38 veterans (half with PTSD and half without) and found myelin in the gray matter of the veterans with PTSD The amount of myelination was increased compared to the amount of myelination in the brains of veterans without PTSD

Meanwhile, colleagues at UC Berkeley found a similar increase in gray matter myelination in adult rats following acute stressful events

For example, veterans with post-traumatic stress disorder (PTSD) and stressed rats exhibiting avoidance behaviors both had increased myelination in the hippocampus, which is often thought to be the center of memory

"To me, these studies in mice and veterans with PTSD," said senior author Thomas Neylan, PhD, director of the VA's PTSD Clinic and Stress and Health Research Program It's really exciting to combine the studies in the population

Humans and mice respond differently to stress

The association between these symptoms and myelinating regions was discovered because UC Berkeley researchers conducted more than a dozen tests on the mice to assess their specific behavioral responses to acute stress

Senior author Daniela Kaufer, professor of integrative biology at UC Berkeley, said: "We know humans have a lot of individual differences, but mice are genetically identical, so you think when you put them under stress, you get the same response

People with PTSD have similar personalities, Neyland said

"There is a lot of heterogeneity in different people with PTSD; it's not one-size-fits-all

The researchers published their findings in December 2021 in the journal Translational Psychiatry

"In the gray matter of the cerebral cortex, most dendrites and axons -- the protrusions of neurons that help communicate with other neurons -- can form thousands of connections, most of which are unmyelinated," Neylan said

Acute stress stimulates oligodendrocytes

In 2014, Kaufer and her colleagues at the University of California, Berkeley, found that mice exposed to acute stress produced more oligodendrocytes in the brain's gray matter—specifically in the hippocampus

Neyland was intrigued by the 2014 discovery and contacted Kaufer, and they have been working together ever since

At the time, scientists looking for changes in myelination associated with brain disease focused on the white matter of the cerebral cortex, which is primarily myelinated
.
In multiple sclerosis, for example, an autoimmune attack destroys the myelin in the white matter
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Coffer may be the first to find evidence of disease-related increased myelination in gray matter
.

Chao and Neylan did find increased myelination of neurons in the gray matter of veterans with PTSD, but not in veterans without PTSD
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The more severe the symptoms, the more severe the myelination
.

This led Koffer and first author Kimberly Long, now a postdoc at UCSF, to see if they could also find an increase in myelin in gray matter after acute trauma in mice
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After they focused on specific symptoms of PTSD in individual rats, they found an association between symptoms and myelination in specific areas of gray matter
.

Xiaolan Zhao then reanalyzed her earlier brain scans of 38 veterans and found the same correlation: specific symptoms were associated with myelination in one area of ​​gray matter, but not in others
.

Long and Kaufer then used a viral gene therapy to speed up a transcription factor called olig1, which increases oligodendrocyte production from stem cells in gray matter
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When Long injected the virus into the dentate gyrus of mice, the researchers found that even in the absence of any stress, the number of oligodendrocytes increased and produced avoidance symptoms
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"The next question is, 'If I change oligodendrocyte formation, do I change behavior?'" Kauf said
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The answer to that question is on this piece of paper, and the answer is yes
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Now, there is still a lot of work to be done to really understand this
.
"

Neylan, Chao and Kaufer are collaborating on further research, including looking for increases in myelin in the brains of deceased PTSD patients, improving functional magnetic resonance imaging of myelin in the brain, and investigating the effects of chronic stress on brain connectivity in mice effects, and use new high-resolution imaging to study myelin deposition in gray matter
.

Journal Reference :

1. Kimberly LP Long, Linda L.
   Chao, Yurika Kazama, Anjile An, Kelsey Y.
   Hu, Lior Peretz, Dyana CY Muller, Vivian D.
   Roan, Rhea Misra, Claire E.
   Toth, Jocelyn M.
   Breton, William Casazza, Sara Mostafavi , Bertrand R.
   Huber, Steven H.
   Woodward, Thomas C.
   Neylan, Daniela Kaufer.
   Regional gray matter oligodendrocyte- and myelin-related measures are associated with differential susceptibility to stress-induced behavior in rats and humans .
   Translational Psychiatry , 2021; 11 (1) DOI: 10.
   1038/s41398-021-01745-5