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Cell-based study reveals that vitamin D can drive the activity of neural stem cells that promote myelin repair

Background

A growing body of evidence demonstrates that vitamin D deficiency is a contributing factor to an increased risk of multiple sclerosis. The link between vitamin D and MS was originally based on the observation that, overall, the prevalence of MS is higher in countries further away from the equator where sun exposure is lower, particularly in the winter months. Since vitamin D is produced in the skin following exposure to sunlight, there is compelling evidence to suggest that people living in countries with relatively low sun exposure are at higher risk of developing MS due to vitamin D deficiency. Indeed, research indicates that individuals living with MS tend to have lower blood levels of vitamin D than healthy individuals.

Vitamin D is hypothesized to protect against MS by directly interacting with genes associated with the immune system, and studies in animals with an MS-like disease show that vitamin D inhibits the disease process through immune-regulating mechanisms. It is unknown, however, if vitamin D plays a role in the repair of nervous tissue damaged by MS by helping to drive remyelination. Neural stem cells are one type of stem cell in the body that can multiply themselves and transform, or differentiate, into mature types of cells of the nervous system, including oligodendrocytes, which are myelin-forming cells. Neural stem cells normally play an important role in neural repair, but their capacity for repair is seriously reduced in MS.

A team of researchers led by Dr. Guang-Xian Zhang and colleagues published a new study in Experimental and Molecular Pathology investigating the role of vitamin D in promoting neural repair by stimulating the growth and maturation of neural stem cells.

The Study

This early pre-clinical study was conducted in cell culture; cells from healthy mouse brain tissue were plated on petri dishes in a growth medium enriched with nutrients, hormones, and growth factors that ensured the survival and vitality of the cells. Neural stem cells were identified with special markers so that they could be counted and monitored.

The authors then examined how neural stem cells are influenced by the presence of calcitriol, which is the hormonally active metabolite of vitamin D (for the purposes of simplicity, calcitriol will be referred to as vitamin D in this article). First, the authors probed the neural stem cells for the presence of receptors that can bind to vitamin D. They subsequently added vitamin D to the cell culture plates to determine if vitamin D can influence the ability of neural stem cells to increase their numbers over the course of several weeks. They also tested the effects of vitamin D on neural stem cell differentiation; that is, their ability to mature into different types of specialized cells of the nervous system, including neuronsastrocytes, and oligodendrocytes. Lastly, they measured changes in the quantities of neurotrophic factors in response to vitamin D; these factors are molecules that drive the survival and differentiation of neural stem cells.

Results

The authors found that neural stem cells carry receptors that can bind to vitamin D. When they added vitamin D to the cell culture plates, the neural stem cells increased their numbers significantly after one week, demonstrating that vitamin D triggers neural stem cells to activate and multiply. Importantly, vitamin D stimulated the neural stem cells to mature into both neurons and myelin-forming oligodendrocytes, but not astrocytes. The mechanism by which vitamin D activated neural stem cells was through promoting increased activity of several important neurotrophic factors.

Comments

This study demonstrated for the first time that vitamin D can promote mechanisms of neural repair by driving the activity of neural stem cells. To date, vitamin D has been investigated for its ability to affect the immune system by interacting with immune-related genes as well as shifting the imbalance between the pro-inflammatory and anti-inflammatory T-cells in the body. This study reveals a novel mechanism by which vitamin D not only curbs the damaging effects of autoimmunity, but may also repair the damage to neurons and the myelin surrounding nerves that results from MS.

This is an example of a very early, pre-clinical study that helps to inform researchers about the molecular and cellular processes underlying the therapeutic benefits of drugs or other compounds; as such, while the results of this study are highly promising, much work remains to be done. The neural stem cells that were examined in this study were from healthy mouse brain tissue, and next steps will entail studying the effects of vitamin D on neural repair in an animal model of an MS-like disease. Unlocking the process by which vitamin D potentially promotes remyelination and brain repair in MS will help inform the multiple ongoing clinical trials investigating the potential of vitamin D supplementation as a therapeutic strategy for MS.

Source

Shirazi HA et al. (2015) 1,25-Dihydroxyvitamin D3 enhances neural stem cell proliferation and oligodendrocyte differentiation. Exp Mol Pathol. 98(2):240-5