New research findings challenge old beliefs about myelin repair in MS
Study reveals myelin-making cells are constantly being produced
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- In a new study, researchers report that myelin-making cells are constantly produced in the brain, challenging old beliefs about myelin repair in MS.
- Aging and inflammation, both common in multiple sclerosis, reduce the survival of these new myelin-producing cells.
- These findings could spur the development of new treatment approaches in MS, according to the research team.
Oligodendrocytes, the cells responsible for making myelin, are constantly being made throughout the brain and spinal cord, even when there’s no myelin damage, according to a new study by U.S. researchers.
These findings challenge the long-held view that oligodendrocyte precursor cells mostly differentiate into oligodendrocytes at sites of damage to drive myelin repair. Instead, this differentiation occurs continuously across the nervous system, and local signals determine which newly formed cells survive and make myelin.
The researchers found that inflammation and aging, which are both prominent in multiple sclerosis (MS), reduced the number of newly formed oligodendrocytes that survived. This suggests that future MS therapies may need to focus not only on generating new myelin-producing cells, but also on promoting their survival and ability to function.
“Leveraging this knowledge … may [ultimately] accelerate our understanding [of oligodendrocytes’ role] in MS and spur the development of new approaches … for therapeutic benefit,” the team wrote.
The study, “Myelin is repaired by constitutive differentiation of oligodendrocyte progenitors,” was published in the journal Science. The work was funded by the National Institutes of Health.
Myelin is a fatty substance that wraps around nerve fibers and helps them send electrical signals. In MS, the immune system launches an inflammatory attack that damages myelin, disrupting normal nerve signaling and ultimately leading to disease symptoms.
Researchers focused on myelin processes in brain
Within the brain and spinal cord, myelin is made mainly by specialized cells called oligodendrocytes. While it is well established that mature oligodendrocytes arise from immature cells called oligodendrocyte precursor cells (OPCs), scientists have long thought that this maturation process was largely triggered by myelin damage.
However, scientists have struggled to track the development of mature oligodendrocytes in living brain tissue, which has limited their ability to test how and when these myelin-making cells are actually made.
In the new study, a team led by researchers from Johns Hopkins University in Baltimore identified a structural change that occurs as OPCs mature into oligodendrocytes, allowing them to follow this process more directly.
Specifically, when OPCs differentiate, they remodel the surrounding extracellular matrix, which is the network of proteins outside cells that helps maintain tissue structure. This leads to the formation of a spherical structure that the researchers termed dandelion clock-like structures (DACS) — because, under a microscope, they resemble a dandelion.
By monitoring the appearance of these structures, the researchers were able to track the growth of OPCs into mature oligodendrocytes across the brain and spinal cord in mice. They found that new oligodendrocytes were constantly being made throughout the nervous system — even when there was no damage to myelin.
Earlier models may have missed some details
Based on these findings, the researchers believe that prior models of OPC development may have missed key details. Contrary to previous assumptions, the data showed that OPCs don’t produce more oligodendrocytes when there’s myelin damage. Instead, they’re constantly differentiating into mature cells, and only the oligodendrocytes that are needed survive to make new myelin.
The rest of the oligodendrocytes simply die off, the researchers found.
“[This work] showed us that OPC differentiation was constantly happening all over the brain,” Dwight Bergles, PhD, coauthor of the study at the Johns Hopkins, said in a university news story. Bergles added that “they seem to have this intrinsic drive to continually try to make new oligodendrocytes.”
The scientist acknowledged that “this may seem very inefficient.” But, he added, “we think this process evolved to provide equal potential to make new oligodendrocytes and myelin anywhere in the brain. It is then left to the neurons to help decide which of these differentiating cells survives to make myelin.”
The researchers also found that OPC differentiation into oligodendrocytes decreased with age and was further suppressed by inflammation. And, when OPCs were damaged, they replicated to maintain a constant pool. However, this response came at the expense of producing fewer mature oligodendrocytes.
According to the team, this could help explain why myelin repair is inefficient in people with diseases such as MS.
Further work is needed to understand the precise biological mechanisms that control the constant differentiation of OPCs into oligodendrocytes, the researchers noted. Such studies, they noted, could uncover important targets for promoting myelin repair.
