Vitamin D in MS

Vitamin D receptor and CYP27B1 (1α-hydroxylase) expression are up-regulated in association with the neuropathology of multiple sclerosis

Joost Smolders, MD, PhD

Vitamin D deficiency is implicated as a risk factor in multiple sclerosis (MS). We studied expression of vitamin D receptor (VDR) and related enzymes in the CNS in relation to MS pathology.

Cortical and hypothalamic neurons stained for VDR and 24-hydroxylase (24-OHase). Accordingly, 1,25(OH)2D3 induced up-regulation of CYP24A1 (encoding 24-OHase) in a SY5Y neuronal cell line. 24-OHase-positive hypothalamic neurons clustered in the periventricular nucleus (PVN) and supraoptic nucleus (SON).

In control and MS normal appearing white matter (NAWM), VDR-staining was observed in oligodendrocyte-like cells, HLA-positive microglia and GFAP-positive astrocytes. 24-OHase staining was restricted to astrocytes in both MS and control NAWM. Accordingly, primary human astrocytes up-regulated VDR and CYP24A1 upon exposure to 1,25(OH)2D3. In both MS and control NAWM, mRNA was detected of VDR, CYP24A1, CYP27B1 (1α-OHase), and LrP2 (Megalin), but not of vitamin D binding protein. Interestingly, a twofold increase in VDR transcripts was found in MS NAWM.

In chronic active MS lesions, HLA-positive microglia/ macrophages and GFAP-positive astrocytes showed VDR staining. Staining for 24-OHase was restricted to astrocytes. VDR and CYP27B1 mRNA expression was increased in active MS lesions. In vitro, TNF-α and IFN-γ up-regulated CYP27B1 mRNA expression in primary human microglia and astrocytes, which may reflect the situation in active lesions.

Increased VDR expression in NAWM in MS and amplified expression of VDR and CYP27B1 in chronic active MS lesions suggest an increased sensitivity to vitamin D in NAWM and an endogenous role for vitamin D metabolism in the control of active lesions in MS.

HLA-positive (**) Microglia in NAWM of control (A) and MS (B) donors showed a nuclear staining for VDR (*). Two-times more VDR-transcripts were found in MS when compared to control NAWM (C).