Multiple Sclerosis Society of Canada

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Early stage study shows that vitamin D can promote myelin repair

Background

Vitamin D is an essential nutrient that provides many health benefits, and a great deal of evidence has recognized vitamin D as a protective factor against the development of multiple sclerosis. In addition to its protective effects, vitamin D has recently been put in the spotlight to uncover if it can help drive remyelination – the process by which specialized cells repair the damage to the myelin that ensheathes nerve fibres in the central nervous system – in people living with MS. Although the body has the innate ability to remyelinate nerve fibres and repair this damage, this ability declines over time as the MS disease process continually attacks myelin, spurring one avenue of research to seek new ways to enhance the body’s remyelination ability.

Oligodendrocytes are the specialized cells that create the myelin sheath; these cells, in turn, are formed from precursor cells called oligodendrocyte progenitor cells (OPC). Previous research has identified a special protein called retinoid X receptor-γ (RXR-γ) that, when activated, helps OPCs rapidly mature into myelin-forming oligodendrocytes. A group of researchers based at the University of Cambridge (UK) noted that RXR-γ only works when it interacts with another protein. This group, together with an international team of collaborators, went on to demonstrate that this unknown protein is the receptor that binds vitamin D. Their findings were published in The Journal of Cell Biology.

The Study

The authors conducted a series of elegant experiments using cellular and molecular techniques to test whether:

  • vitamin D receptors are commonly found in brain lesions in people living with MS, compared to normal brain tissue from healthy individuals;
  • vitamin D receptors interact with RXR-γ in OPCs and oligodendrocytes grown in cell culture;
  • vitamin D receptors are present during remyelination by examining brain tissues from rats in which demyelination was experimentally triggered;
  • blocking vitamin D receptors on OPCs would affect the maturation of OPCs into myelin-forming oligodendrocytes and, consequently, lead to impaired remyelination;
  • activating vitamin D receptors by adding vitamin D could improve the maturation of OPCs and enhance remyelination.

Results

The authors found that vitamin D receptors are significantly more widespread in MS lesions – particularly new, active lesions – compared to healthy brain tissue in humans.

By looking at cells grown in culture, they found that the vitamin D receptor interacts with the remyelination-promoting RXR-γ protein in myelin-forming cells, and that this receptor is active during the stages of remyelination in rats that have an MS-like disease.

When the authors blocked vitamin D receptors from binding vitamin D and functioning correctly, this prevented OPCs from maturing properly into myelin-forming oligodendrocytes. As expected, this led to impaired remyelination in rats with the MS-like disease. At the other end of the spectrum, activating these receptors with vitamin D led to improved remyelination.

Comment

These findings support a study from earlier this year that demonstrated that vitamin D can stimulate neural stem cells into becoming both myelin-producing oligodendrocytes and new nerve cells. This study went several steps further by showing that stimulating these cells with vitamin D can repair myelin in animals with an MS-like disease, and went on to dissect out the precise mechanisms by which vitamin D carries out its remyelinating actions.

While this study is still an early investigation into the remyelination capabilities of vitamin D, it adds to a growing body of scientific evidence showing that vitamin D might have potential therapeutic benefits beyond influencing the risk of developing MS. As the authors state, “further investigation into the molecular mechanisms of [vitamin D receptors] in remyelination will open up new opportunities for the development of regenerative medicines for demyelinating diseases.” Specifically, these findings will help to inform the design and interpretation of clinical trials studying the safety and effectiveness of vitamin D supplementation for treating the symptoms and/or disease course of MS, since smaller scale trials to date have led to mixed results (see our Vitamin D page for more details).

Source

de la Fuente AG et al. Vitamin D receptor-retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation. J Cell Biol. 2015; 211(5):975-85.