Mouse study finds some brain regions recover better after myelin damage
Findings may help explain patterns of damage seen in multiple sclerosis
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A brain map highlights regions studied for myelin damage and repair. (Photo from iStock)
- New research creates detailed brain-wide maps of oligodendrocytes, the cells that make myelin.
- Oligodendrocytes show different levels of vulnerability and recovery after myelin injury in mice.
- Understanding these regional differences may help guide future research into multiple sclerosis and other myelin disorders.
Myelin-making cells in some areas of the brain were more resistant to injury in a mouse model of myelin damage than the same cells in other brain regions.
Researchers created detailed, brain-wide maps showing exactly where myelin-making cells, known as oligodendrocytes, are located in the brain. Using these maps, they were able to evaluate how these cells change with age and after myelin injury in laboratory models.
The findings may help researchers better understand neurological disorders such as multiple sclerosis (MS), which is marked by inflammation that damages myelin.
The study, “Brain-wide mapping of oligodendrocyte organization, oligodendrogenesis, and myelin injury,” was funded by the National Institutes of Health (NIH) and published in Cell.
Why myelin matters in brain health
Myelin is a fatty substance that wraps around nerve fibers and helps them send electrical signals more efficiently, much like rubber insulation around a metal wire. When myelin is damaged or destroyed, nerves cannot transmit signals as effectively, a process that contributes to MS symptoms.
Oligodendrocytes are the brain cells responsible for producing myelin, and understanding how they work is important for efforts aimed at repairing myelin.
Research has shown that myelin content varies across brain regions. Scientists believe these differences may be linked to variations in oligodendrocyte numbers, but they have struggled to develop detailed maps showing exactly where these myelin-making cells are located.
In this new study, researchers at Johns Hopkins University developed a novel imaging and analysis pipeline that allowed them to pinpoint oligodendrocytes with greater precision.
“Because myelin can speed communication between neurons, these maps of regional differences in myelin patterning may help us understand how different parts of the brain accomplish different tasks,” Dwight Bergles, PhD, co-author of the study at the Johns Hopkins University School of Medicine, said in a university news story.
How researchers mapped myelin-making cells
The pipeline involved treating brain samples to remove fatty deposits that can make it harder to image deep brain regions, then scanning them with advanced microscopes. The data were analyzed with machine learning tools to generate comprehensive maps of oligodendrocytes across the brain. The researchers also integrated these findings with information about gene activity and the structure of nerve cells.
“Our study identifies not only the location of oligodendrocytes in the brain, but also integrates information about gene expression and the structural features of neurons,” Bergles said. “It’s like mapping the location of all the trees in a forest, but also adding information about soil quality, weather and geology to understand the forest ecosystem.”
Using their pipeline, researchers showed that oligodendrocyte patterns were nearly identical on the left and right sides of the brain. These patterns also changed as the mice aged. For example, the neocortex and hippocampus, brain regions involved in complex thought and memory, showed a notable increase in oligodendrocyte numbers over time.
The researchers noted that oligodendrocyte patterns varied slightly among mouse strains with different genetic backgrounds, likely due to differences in early myelin development. But within the same strain, patterns were highly consistent across individual mice. The team also reported no notable differences between male and female mice in the analyses they conducted.
The team also tested how oligodendrocyte patterns were affected after treatment with cuprizone, a toxin that damages myelin. Cuprizone exposure is commonly used in laboratory studies as a model of myelin injury.
Some brain regions recover better than others
Results showed that, in the cuprizone model, oligodendrocytes in some brain regions were more severely affected than others. For example, the density of oligodendrocytes in the neocortex and hippocampus decreased sharply after cuprizone exposure and showed minimal or less robust recovery afterward.
Oligodendrocyte counts in other brain areas involved in processing sensation also dropped sharply after cuprizone treatment, but they recovered more quickly.
“Together, these findings highlight that there are strong regional influences on oligodendrocyte vulnerability, resilience, and regenerative potential,” the researchers wrote, noting that these findings may help guide future research into diseases such as MS.
More broadly, the researchers said their platform could provide scientists with a new tool to better understand oligodendrocyte biology. To help accelerate discovery, their maps have been made freely available to other researchers.
“It will be interesting to use this approach to see how different life experiences, such as stress, social interaction, and learning affect these patterns,” Bergles said.
