Sunday, 22 February 2015

ClinicSpeak: vitamin D promoting neural stem cells

Should we studying vD as a putative neurorestorative agent? #MSBlog #MSResearch #ClinicSpeak

"The study below suggests that vD has positive effects on neural stem cells (NSCs) and therefore may have a role to play in recovery from MS relapses. vD increases the proliferation of NSCs that then differentiate into neurons and oligodendrocytes that make myelin. Could this be relevant to recovery from relapses in MS? Could MSers who are vD sufficient, or replete, more likely to recover from relapses? This can be studied in vivo (within the body); there are some MRI techniques that can be used to measure remyelination in focal MS lesions. The problem with this however is low vD levels have been linked to inflammation; one could argue that the low vD levels results in more severe focal inflammation and hence more damage. It will be difficult to tease out the disparate effects of vD biology, therefore it may be better to study vD's putative effect on remyelination in a 'non-inflammatory' demyelinating animal model; we have the ability to make animals vD deficient by feeding them on a special diet."


"Please don't forget reverse causation; i.e inflammation causes the low vD levels and not the other way round. Almost all inflammatory diseases are associated with low vD levels. Most epidemiologists I speak to don't buy that low vD levels drive inflammation in MS. They say the association is too weak and too non-specific. Please note this statement refers to MS disease activity in established MS and not to vD as a putative preventive strategy. Most epidemiologists acknowledge the only way to sort this out is to do a large population-based vD supplementation study."

"We recommend all our patients with MS take vD supplements with the aim of making them vD replete. The rationale for the this is not because there is evidence that vD is disease modifying, but for bone health. We know that MSers are more likely to be have thin bones (osteopaenia and/or osteoporosis) and are high risk of falls and fractures. vD supplements have been shown to have a positive impact on bone health, albeit in elderly females. What really needs to be done is a national study on vD supplements in MSers to see if it has a positive impact on bone health. It is not ideal to translate data, or evidence, generated in one population to another population."


Epub: Shirazi et al. 1,25-dihydroxyvitamin D3 enhances neural stem cell proliferation and oligodendrocyte differentiation. Exp Mol Pathol. 2015 Feb 10. pii: S0014-4800(15)00023-4. doi: 10.1016/j.yexmp.2015.02.004.

Background: 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has recently been found to suppress experimental autoimmune encephalomyelitis (EAE), an animal model of MS.Although its effect was attributed to an anti-inflammatory mechanism, it is not clear whether this treatment can also directly act on neural cells to promote CNS recovery. 


Objective: The present study investigates the effect of various concentrations of 1,25(OH)2D3 on neural stem cell (NSC) proliferation and their differentiation to oligodendrocytes, the myelinating cells. 

Results: We have, for the first time, shown that NSCs constitutively express vitamin D receptor (VDR), which can be upregulated by 1,25(OH)2D3. This vitamin significantly enhanced proliferation of NSCs, and enhanced their differentiation into neurons and oligodendrocytes, but not astrocytes. NSCs treated with 1,25(OH)2D3 showed increased expression of NT-3, BDNF, GDNF and CNTF, important neurotrophic factors for neural cell survival and differentiation. 

Conclusions: Overall, we demonstrated that 1,25(OH)2D3 has a direct effect on NSC proliferation, survival, and neuron/oligodendrocyte differentiation, thus representing a novel mechanism underlying its remyelinating and neuroprotective effect in MS/EAE therapy

10 comments:

  1. Assuming reverse causality what is the mechanism by which inflammation cause vitamin d levels to drop? It is unlikely to be a reduction in supply, the inflammation stops summer midday sun exposure or alters diet, that would require severe disability.

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  2. Prof G the evidence for a vitamin d prevention effect in Ms is getting weaker. Month of birth, maternal half sib effect has all been proved wrong.

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    1. Why would there be a month of birth effect, unless vitamin d level only has an effect at one particular point in gestation. I would thought there would be more an effect of how sunny the summer was that year, assuming the sun is not avoided.

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    2. Month of birth effect has not been proved wrong; just questioned. It needs a more detailed study. The vD prevention hypothesis is not based on MoB or the half-sib data. There are many more factors than this that suggest MS is linked to low vD levels. The strongest being the latitude effect. Is the latter due to vD deficiency or lack of sunshine or both?

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  3. or ice-cream as MD so eloquently put it. could be anything prof g, doesn't have to be vd

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    1. Except that ice cream consumption does not fit the epidemiology as ice cream consumption does not match to latitude.

      The real problem with this work is that it uses 1,25(OH)D. The level of 1,25(OH)D in the blood is fixed as it controls the blood calcium level. It is if anything higher in people with vitamin d deficiency. It is 25(OH)D that changes with vitamin d consumption and so it is that which should be tested.

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    2. I think you maybe taking the comment too literally http://www.tylervigen.com/ spurious correlations

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    3. I was making a point about a flippant statement. 25(OH)D3 has been shown to be important to the immune system. There are vitamin d receptors in cells. Immune cells can convert 25(OH)D to 1,25(OH)D and this is for a purpose. In biology, rather than medicine, it is accepted that vitamin d affects more than calcium in the body. The same is true in animal husbandry.

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  4. I hate to bring this up again but is there one of you guys that can find a study or trail that was done 30-40 years ago that was done pertaining stress in monkeys brains that had ms and there findings proved there where veins not letting the vt d get to where it's so post to go. I had read it just cant find it again

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    1. Dear Bill,
      Monkeys do not get MS as far as we know, I am not familiar with the study maybe one of the readers can help out

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