Molecular Neurobiology

, Volume 47, Issue 3, pp 946–956 | Cite as

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

  • Mingchong Yang
  • Zhaoyu Qin
  • YanYan Zhu
  • Yun Li
  • Yanjiang Qin
  • Yongsheng Jing
  • Shilian Liu
Article

Abstract

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.

Keyword

Secondary progressive multiple sclerosis Cerebrospinal fluid Vitamin D-binding protein Experimental allergic encephalomyelitis Vitamin D 

Abbreviations

SPMS

Secondary progressive multiple sclerosis

EAE

Experimental allergic encephalomyelitis

2-D DIGE

Two-dimensional fluorescence difference in-gel electrophoresis

DBP

Vitamin D-binding protein

Supplementary material

12035_2012_8387_MOESM1_ESM.doc (1.7 mb)
ESM 1DOC 1,726 kb

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Mingchong Yang
    • 1
  • Zhaoyu Qin
    • 2
  • YanYan Zhu
    • 1
  • Yun Li
    • 3
  • Yanjiang Qin
    • 4
  • Yongsheng Jing
    • 5
  • Shilian Liu
    • 1
  1. 1.Institute of Biochemistry and Molecular Biology, School of MedicineShandong UniversityJinanPeople’s Republic of China
  2. 2.Laboratory of Systems Biology, Institute of Biomedical SciencesFudan UniversityShanghaiChina
  3. 3.Department of Clinical LaboratoryAffiliated Hospital of Shandong University of Traditional Chinese MedicineJinanChina
  4. 4.Department of NeurologyQilu Hospital of Shandong UniversityJinanChina
  5. 5.Jinan Central Hospital Affiliated to Shandong UniversityJinanChina

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