Immature Myelin-Making Cells Can Trigger Inflammation, Says New Report Funded by National MS Society
April 15, 2019
- Researchers report finding that immature myelin-making cells can form abnormal clusters on blood vessels in the brains of people with MS. Studies in mice also reveal that, instead of migrating to form new myelin, these cells disrupt the blood-brain barrier that normally protects the brain and spinal cord from damage, and also trigger immune system activity in the brain.
- Opening a research focus on the understudied area of the interactions between blood vessels and oligodendrocytes may help to identify therapeutic opportunities that could both slow down or stop myelin damaging immune activity and promote repair in MS.
- The team (Stephen Fancy, PhD, DVM, University of California, San Francisco, and colleagues) published their findings in Nature Neuroscience. (published online April 15) Dr. Fancy is a Harry Weaver Neuroscience Scholar of the National MS Society.
In multiple sclerosis, myelin sheaths that insulate nerve fibers are damaged, and so are myelin-making cells called oligodendrocytes. The loss of myelin makes nerve fibers more vulnerable to injury. These myelin sheaths can be regenerated in a process called remyelination or myelin repair. Remyelination by immature oligodendrocyte precursor cells (OPCs) is critical to recovery, but myelin repair often fails, especially in the later stages of MS, contributing to disease progression. Myelin repair generally involves two stages: First, OPCs are recruited to migrate into the area of damage (lesion) from surrounding brain areas, and then the OPCs develop (“differentiate”) into mature oligodendrocytes within the lesion and start to make myelin.
A team led by Dr. Stephen Fancy at the University of California, San Francisco, investigated the idea that interactions with blood vessels that make up the “blood-brain barrier” may influence the ability of OPCs to both migrate and also properly differentiate to repair lesions. The blood-brain barrier is a system of blood vessels that controls what can enter the brain from the bloodstream, and research indicates that this barrier is disrupted early in MS, facilitating the immune response that targets the brain and spinal cord.
Dr. Fancy’s team used sophisticated microscopic imaging to examine the remyelination process in mice and in brain tissue obtained from people with MS via autopsy. They explored the possibility that OPCs use the blood vessels in the brain as a climbing frame to crawl around on and gain access to areas of damage.
The researchers observed abnormal clusters of OPCs in blood vessels near areas of active inflammation in MS tissues. To explore whether such clusters interfered with OPC migration and with blood-brain barrier integrity, they conducted extensive experiments in mice with an MS-like disease. The studies show that OPC clustering along blood vessels reduces their ability to migrate to areas of damage. Also, these OPCs interfere with several aspects of blood-brain barrier integrity, causing certain cells to be displaced and others to dysfunction – thus increasing this barrier’s leakiness and triggering inflammation in the brain.
The team published their findings in Nature Neuroscience. (published online April 15
) Dr. Fancy is a Harry Weaver Neuroscience Scholar of the National MS Society.
Opening a research focus on the understudied area of the interactions between blood vessels and oligodendrocytes may help to identify new therapeutic opportunities for promoting myelin repair in MS.
Read more about repairing damage in MS