Oligodendrocyte Precursor Cells Disrupt Blood-brain Barrier, Trigger Brain Inflammation in MS, Study Shows

Oligodendrocyte Precursor Cells Disrupt Blood-brain Barrier, Trigger Brain Inflammation in MS, Study Shows

Oligodendrocyte precursor cells (OPCs), the cells responsible for myelin production, are unable to migrate into sites of myelin loss in the brain. These cells then cluster and disrupt the blood-brain barrier (BBB), triggering an inflammatory process in the early stages of multiple sclerosis (MS), a study shows.

The study, “Aberrant oligodendroglial–vascular interactions disrupt the blood–brain barrier, triggering CNS inflammation,” was published in the journal Nature Neuroscience.

MS is an autoimmune disease characterized by the loss of myelin (demyelination) — the fat-rich substance that protects nerve fibers — which leads to neurodegeneration. Along with loss of myelin, researchers have observed that the blood-brain barrier — a highly selective membrane that shields the central nervous system with its cerebrospinal fluid from the general blood circulation — breaks down in the initial stages of disease.

A team led by researchers at the University of California, San Francisco, have now discovered that OPCs are involved in the disruption of the blood-brain barrier in MS, according to a press release from the National MS Society, which funded the study.

Oligodendrocytes are myelin-producing cells and are responsible for myelinating the nerve cells’ axons — a single oligodendrocyte is capable of myelinating multiple axons. Mature myelin-producing oligodendrocytes develop from more immature, stem cell-like OPCs.

In a normal brain, upon myelin loss, OPCs are called into action and travel into the damage site where they mature and generate myelin-producing oligodendrocytes.

In this study, the researchers found that OPCs in MS form clusters in blood vessels of the brain-blood barrier, having lost the ability to detach from these vessels and migrate to injury sites.

In an animal model of MS, they saw that OPC aggregates altered the location of other cells — called astrocytes — in a competition for space, and contributed to the disruption of blood vessels. Astrocytes are a group of star-shaped cells, belonging to the group of glial cells, that provide neurons with energy, and work as a platform to clean up their waste. They also have other functions within the brain, such as regulating blood flow and inflammation.

The team also observed that OPC aggregates trigger an immune inflammatory response, shown by a large number of microglia (the central nervous system immune cells) and immune cells called macrophages around these cell clusters.

“We find in several MS cases, in lesion areas with active inflammation, that OPCs can be found clustered on vasculature, representing a defect in single cell perivascular migration and inability to detach from blood vessels,” the researchers wrote.

Further molecular analysis revealed that OPCs have high levels of Wnt signaling, and elevated secretion of Wif1 factor to the extracellular space that could explain why OPCs accumulate and destroy the blood-brain barrier.

The WiF1 factor is actually a negative regulator of Wnt signaling that is essential for the maintenance of the blood-brain barrier structure. This factor competes with Wnt ligands, and affects the integrity of cellular junctions, making the blood-brain barrier more fragile and permeable.

“Evidence for this defective oligodendroglial–vascular interaction in MS suggests that aberrant OPC perivascular migration not only impairs their lesion recruitment but can also act as a disease perpetuator via disruption of the BBB,” the researchers wrote.

They suggested that more studies are needed to better understand the interactions between blood vessels and oligodendrocytes, which could help identify new therapeutic targets for promoting myelin repair in MS.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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3 comments

  1. Brent McMillan says:

    The biggest problem I see with MS living in Oregon is the fact that a Doctor won’t diagnose it. Not only do they provide terrible medical practice, terrible bed side manner and do not listen to a word you say!! These MS doctors are so far behind the times here that they are using standards from the early 2000’s and equipment that may be older to diagnose MS!!
    The standards are ridiculous as they ignore the symptoms!! You need 5 lesions in the right spot, 90% of testing results, O-Bands and other markers in body fluid tests. You need the right or standard inflammation as 75% of Ms patience. A torn cuticle on the left pinky!! They have made it to where severe MS patience like my Brother and I do not fit the normal here so No,No,No MS. I am 5 years undiagnosed MS from Chemical Exposure. Then MY Doctor told me that MS and other Autoimmune can’t be caused by Chemical Exposure.

  2. Elaine Werder-Coleman says:

    Thank you to anyone who donates to the MS SOCIETY and to all the researchers for trying to find a cure. It’s good knowing we are NOT forgotten. Interesting find, hard to completely understand but I am truly grateful that you are continuing research.

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