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Expression of vitamin d receptor and metabolizing enzymes in multiple sclerosis-affected brain tissue.
MedLine Citation:
PMID:  23334593     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
ABSTRACT: Vitamin D deficiency has been implicated as a risk factor for multiple sclerosis (MS), but how vitamin D metabolism affects MS pathophysiology is not understood. We studied the expression of vitamin D receptor (VDR) and related enzymes, including 1,25(OH)2D-24-hydroxylase (24-OHase; CYP24A1) and 25(OH)D-1α-hydroxylase (CYP27B1), in CNS tissues of 39 MS patients and20 controls and in primary human glial cells in vitro. In control and MS normal-appearing white matter (NAWM), nuclear VDR immunostaining was observed in oligodendrocyte-like cells, humanleukocyte antigen (HLA)-positive microglia, and glial fibrillary acidic protein-positive astrocytes. There was a 2-fold increase in VDR transcripts in MS NAWM versus control white matter (p = 0.03). In chronic active MS lesions, HLA-positive microglia/macrophages showed nuclear VDR staining; astrocytes showed nuclear and cytoplasmic VDR staining. Staining for 24-OHase was restricted to astrocytes.VDR and CYP27B1 mRNA expressions were increased in active MS lesions versus NAWM (p < 0.01, p = 0.04, respectively). In primary human astrocytes in vitro, the active formof vitamin D, 1,25(OH)2D3, induced upregulation of VDR and CYP24A1. Tumor necrosis factor and interferon-γ upregulated CYP27B1 mRNA in primary human microglia and astrocytes. IncreasedVDR expression in MS NAWM and inflammatory cytokine-induced amplified expression of VDR and CYP27B1 in chronic active MS lesions suggest increased sensitivity to vitamin D in NAWM and a possible endogenous role for vitamin D metabolism in the suppression of active MS lesions.
Authors:
Joost Smolders; Karianne G Schuurman; Miriam E van Strien; Jeroen Melief; Debbie Hendrickx; Elly M Hol; Corbert van Eden; Sabina Luchetti; Inge Huitinga
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neuropathology and experimental neurology     Volume:  72     ISSN:  1554-6578     ISO Abbreviation:  J. Neuropathol. Exp. Neurol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985192R     Medline TA:  J Neuropathol Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  91-105     Citation Subset:  IM    
Affiliation:
From the Neuroimmunology Research Group (JS, KGS, JM, DH, CVE, SL, IH), and Astrocyte Biology and Neurodegeneration Research Group (MEVS, EMH), Netherlands Institute for Neuroscience, Amsterdam, The Netherlands; and Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands (EMH).
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