Molecular Neurobiology

, Volume 47, Issue 3, pp 946–956

Vitamin D-binding Protein in Cerebrospinal Fluid is Associated with Multiple Sclerosis Progression


  • Mingchong Yang
    • Institute of Biochemistry and Molecular Biology, School of MedicineShandong University
  • Zhaoyu Qin
    • Laboratory of Systems Biology, Institute of Biomedical SciencesFudan University
  • YanYan Zhu
    • Institute of Biochemistry and Molecular Biology, School of MedicineShandong University
  • Yun Li
    • Department of Clinical LaboratoryAffiliated Hospital of Shandong University of Traditional Chinese Medicine
  • Yanjiang Qin
    • Department of NeurologyQilu Hospital of Shandong University
  • Yongsheng Jing
    • Jinan Central Hospital Affiliated to Shandong University
    • Institute of Biochemistry and Molecular Biology, School of MedicineShandong University

DOI: 10.1007/s12035-012-8387-1

Cite this article as:
Yang, M., Qin, Z., Zhu, Y. et al. Mol Neurobiol (2013) 47: 946. doi:10.1007/s12035-012-8387-1


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 scavenge 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.


Secondary progressive multiple sclerosisCerebrospinal fluidVitamin D-binding proteinExperimental allergic encephalomyelitisVitamin D



Secondary progressive multiple sclerosis


Experimental allergic encephalomyelitis


Two-dimensional fluorescence difference in-gel electrophoresis


Vitamin D-binding protein

Supplementary material

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© Springer Science+Business Media New York 2013