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Brain cells can probably activate Vitamin D without liver or kidney (at least in rats) – Sept 2017

Differential expression of vitamin D-associated enzymes and receptors in brain cell subtypes

The Journal of Steroid Biochemistry and Molecular Biology. online 8 Sept. 2017, https://doi.org/10.1016/j.jsbmb.2017.09.008
Véréna Landela, Delphine Stephana, Xiaoying Cuib, Darryl Eylesb, c, François Ferona, ,

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• In comparison to the kidney and liver, the brain produces low levels of the transcripts coding for the enzymes Cyp27a1, Cyp27b1, Cyp24a1.
• High levels of Pdia3 mRNA are found in cortex and hippocampus compared to kidney and liver.
• The transcript coding for Vdr, the genomic vitamin D receptor, is mainly expressed in astro cytes.
• The strongest expression of Pdia3 mRNA is observed in neurons, astrocytes and endothelial cells.
• An increased production of Cyp24a1 is found in microglia and endothelial cells after treatment with 1,25(OH)2D3.
• In the brain, Pdia3 may be considered as the main vitamin D receptor.

Accumulating evidence indicates that the active form of vitamin D, 1,25(OH)2D3, can be considered as a neurosteroid. However, the cerebral expression of vitamin D-associated enzymes and receptors remains controversial. With the idea of carrying out a comparative study in mind, we compared the transcript expression of Cyp27a1, Cyp27b1, Cyp24a1, Vdr and Pdia3 in purified cultures of astrocytes, endothelial cells, microglia, neurons and oligodendrocytes. We observed that endothelial cells and neurons can possibly transform the inactive cholecalciferol into 25(OH)D3. It can then be metabolised into 1,25(OH)2D3, by neurons or microglia, before being transferred to astrocytes where it can bind to VDR and initiate gene transcription or be inactivated when in excess. Alternatively, 1,25(OH)2D3 can induce autocrine or paracrine rapid non-genomic actions via PDIA3 whose transcript is abundantly expressed in all cerebral cell types. Noticeably, brain endothelial cells appear as a singular subtype as they are potentially able to transform cholecalciferol into 25(OH)D3 and exhibit a variable expression of Pdia3, according to 1,25(OH)2D3 level. Altogether, our data indicate that, within the brain, vitamin D may trigger major auto-/paracrine non genomic actions, in addition to its well documented activities as a steroid hormone.

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