Yang M, Qin Z, Zhu Y, Li Y, Qin Y, Jing Y, Liu S.Mol Neurobiol. 2013 Jan 22. [Epub ahead of print]
Multiple sclerosis is a neurological disorder that presents with symptoms including inflammation, neurodegeneration, and demyelination of the central nervous system (CNS). Secondary progressive multiple sclerosis (SPMS) manifests with serious physical disability. To quantitatively analyze differential protein expression in patients with SPMS, we performed two-dimensional fluorescence difference in-gel electrophoresis, followed by mass spectrometry on the cerebrospinal fluid of these patients and patients with other neurological diseases. Vitamin D-binding protein (DBP), gelsolin, albumin, etc. showed more than a 1.5-fold difference between the two groups. Based on these results, an experimental allergic encephalomyelitis (EAE) model of multiple sclerosis in Lewis rats was used to investigate DBP's role in the disease. Protein levels, mRNA transcripts, and ligands of DBP in different regions of the CNS were evaluated under various vitamin D intake levels. Here, DBP levels increased in the experimental rat groups compared to the control groups regardless of vitamin D intake. Moreover, DBP mRNA levels varied in different parts of the CNS including spinal cords in the experimental groups. The observed differences between DBP protein and mRNA levels in the experimental groups' spinal cords could be derived from the disruption of the blood-brain barrier. Furthermore, an interaction between DBP and actin was confirmed using coimmunoprecipitation and western blot. These results indicate a role for DBP in the actin scavenger system. Moreover, in the experimental group that received oral vitamin D3 supplement, we observed both delayed onset and diminished severity of the disease. When DBP was upregulated, however, the benefits from the vitamin D3 supplements were lost. Thus, we inferred that high levels of DBP were adverse to recovery. In conclusion, here we observed upregulated DBP in the cerebrospinal fluid could serve as a specific diagnostic biomarker for the progression of multiple sclerosis. Next, we demonstrate the vital function of increased levels of free vitamin D metabolites for multiple sclerosis treatment. Finally, vitamin D supplements may be particularly beneficial for SPMS patients.
In this study they find higher levels of a vitamin D binding protein (VD-BP) in the spinal fluid of SPMSers but do not report on RRMSers. To work out the significance of this they turn to the Lewis rat EAE model which gets one attack and fully recovers and shows little to no never loss or demyelination and so at best reflects an attack but not really progressive MS. When cells and blood proteins are entering the spinal cord there are difference in VD-BP, but this is true of many many proteins and in many cases this is simply a refection of the different type of cell entering the CNS, which have different protein contents. The VD-BP was associated with actin which is the skeleton of cells. When rats were supplemented with Vitamin D they were protected but if they left it too late such that the changes including accumulation of VD-BP then it did not work. It could well be that VD-BP protein that binds to vitamin D will inhibit its function, but the immune function that is being effected here could easily be in the blood rather than the brain.
However, they inferre that high levels wer adverse to recovery. However the problem of this causal relationship. Because disease in Lewis rats recovers so the high level of VD-BP does not stop recovery, in rats, and I would bet it is temporal in that it will diminish in the spinal cord when animals recover. The treatment effect observed here is on the immune system and this does not appear to be the major player in SPMS. Lewis rat EAE is as close to progressive MS as my toe is to my nose, so be very, very cautious about how you interpret this abstract because the conclusions are not varified.
Whilst we do argue that people should be vitamin D replete especially in SPMS as we want you to have good bone health. This research has some way to go before a causal relationship can be estalished and adding extra vitamin d in this context is to use vitamin D to be a mop for the VD-BP.