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Vitamin D metabolism in the nervous system: potential effects of glucocorticoids
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Several studies have reported that neuronal function is influenced by vitamin D and it has been proposed that low serum 25-hydroxyvitamin D3 levels may be a risk factor for several brain disorders. However, little is known about the activation and metabolism as well as mechanisms of action of vitamin D in the neurons. In a previous study, we reported that the mouse motor neuron-like hybrid cell line NSC-34 expresses mRNA for CYP24A1 as well as the CYP24A1-mediated enzyme activity (Almokhtar et al., 2016). In contrast, the present results show that neither mRNA expression nor enzymatic activities of vitamin D3 metabolizing CYP enzymes could be detected in primary neuron-enriched cells from rat embryonic cortex. However, the levels of 25-hydroxyvitamin D3 incubated with cultured primary cells decreased substantially, indicating metabolism of this substrate. NSC-34 cells were found to produce, besides 24,25-dihydroxyvitamin D3, a major as yet unknown 25-hydroxyvitamin D3 metabolite in addition. The current results indicate drug-mediated regulation of vitamin D3 metabolism in cells of the nervous system. The results showing effects of prednisolone on expression of CYP24A1 mRNA, CYP24A1-mediated hydroxylase activity and 25-hydroxvitamin D3 consumption in NSC-34 cells are all consistent with an increased 25-hydroxyvitamin D3 metabolism. The results indicate that therapeutic treatment with glucocorticoids may lead to a potential decrease in active forms of vitamin D3 in brain cells. It might be speculated that administration of corticosteroids leading to reported CNS adverse effects may at least in part be due to effects of glucocorticoids on vitamin D3 metabolism.

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Chemical Sciences Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-333917OAI: oai:DiVA.org:uu-333917DiVA: diva2:1158236
Available from: 2017-11-18 Created: 2017-11-18 Last updated: 2017-11-19
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Almokhtar, MokhtarWikvall, KjellNorlin, Maria
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