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

Landel, Véréna; Stephan, Delphine; Cui, Xiaoying; Eyles, Darryl W.; Féron, François

doi:10.1016/j.jsbmb.2017.09.008

Cited by 91 publications

(73 citation statements)

References 25 publications

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“…Within the neurovascular unit, CYP27A1, CYP27B1 and CYP24A1 expressions have been confirmed in astrocytes, endothelial cells, microglia, oligodendrocytes and notably, with significant expression of CYP27B1 particularly indicated in neurons (75) . However, differential expression of the VDR binding proteins has been described.…”

Section: Cellular Distribution Of Vitamin D Receptor and Associated Ementioning

confidence: 90%

“…1). VDR immunoreactivity was indicated within (62,70,73,75,130) . Activation of VDRE promotes expression of vascular endothelial growth factor (VEGF) (234) which is located throughout the brain including astrocytes (235) , neurons (236) , oligodendrocytes (237) , microglial cells (238) and the endothelium at the BBB (239) .…”

Section: Vitamin D Receptors and The Cytochrome P450 Enzymes In Brainmentioning

confidence: 99%

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Genetic, environmental and biomarker considerations delineating the regulatory effects of vitamin D on central nervous system function

et al. 2019

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Studies show that vitamin D (vit-D) (25(OH)D), the bioactive metabolite (1,25(OH)2D3) and vit-D receptors (vit-D receptor; protein disulphide isomerase, family A member 3) are expressed throughout the brain, particularly in regions pivotal to learning and memory. This has led to the paradigm that avoiding vit-D deficiency is important to preserve cognitive function. However, presently, it is not clear if the common clinical measure of serum 25(OH)D serves as a robust surrogate marker for central nervous system (CNS) homeostasis or function. Indeed, recent studies report CNS biosynthesis of endogenous 25(OH)D, the CNS expression of the CYP group of enzymes which catalyse conversion to 1,25(OH)2D3 and thereafter, deactivation. Moreover, in the periphery, there is significant ethnic/genetic heterogeneity in vit-D conversion to 1,25(OH)2D3 and there is a paucity of studies which have actually investigated vit-D kinetics across the cerebrovasculature. Compared with peripheral organs, the CNS also has differential expression of receptors that trigger cellular response to 1,25(OH)2D3 metabolites. To holistically consider the putative association of peripheral (blood) abundance of 25(OH)D on cognitive function, herein, we have reviewed population and genetic studies, pre-clinical and clinical intervention studies and moreover have considered potential confounders of vit-D analysis.

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Section: Cellular Distribution Of Vitamin D Receptor and Associated Ementioning

confidence: 90%

Section: Vitamin D Receptors and The Cytochrome P450 Enzymes In Brainmentioning

confidence: 99%

Genetic, environmental and biomarker considerations delineating the regulatory effects of vitamin D on central nervous system function

et al. 2019

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“…Considering that its presence in the brain is greater than VDR, it has been suggested that would have a greater role in the CNS disorders (Tohda, Urano, Umezaki, Nemere, & Kuboyama, ) since it is present in practically all cell types and acts in nongenomic functions of the VD. There is no previous information on the influence of variants on the PDIA3 gene in MS (Landel, Sthefan, Cui, Eyles, & Feron, ). We observed only two variants of PDIA3 gene in our cohort but no associations were observed in MS or AID groups.…”

Section: Discussionmentioning

confidence: 99%

Exonic variants of genes related to the vitamin D signaling pathway in the families of familial multiple sclerosis using whole‐exome next generation sequencing

et al. 2019

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Introduction Vitamin D (VD) deficiency has been associated with multiple sclerosis (MS) and other autoimmune diseases (AIDs). However, the effect of the genetics of VD on the risk of MS is subject to debate. This study focuses on genes linked to the VD signaling pathway in families with MS. The evaluation of gene variants in all the members of families could contribute to an additional knowledge on the information obtained from case‐control studies that use nonrelated healthy people. Material and Methods We studied 94 individuals from 15 families including at least two patients with MS. We performed whole‐exome next generation sequencing on all individuals and analyzed variants of the DHCR7, CYP2R1, CYP3A4, CYP27A1, GC, CYP27B1, LRP2, CUBN, DAB2, FCGR, RXR, VDR, CYP24A1, and PDIA3 genes. We also studied PTH, FGF23, METTL1, METTL21B, and the role of the linkage disequilibrium block on the long arm of chromosome 12, through analysis of the CDK4, TSFM, AGAP2, and AVIL genes. We compared patients with MS, other AIDs and unaffected members from different family types. Results The study described the variants in the VD signaling pathway that appear in families with at least two patients with MS. Some infrequent variants were detected in these families, but no significant difference was observed between patients with MS and/or other AIDs and unaffected family members in the frequency of these variants. Variants previously associated with MS in the literature were not observed in these families or were distributed similarly in patients and unaffected family members. Conclusion The study of genes involved in the VD signaling pathway in families that include more than one patient with MS did not identify any variants that could explain the presence of the disease, suggesting that VD metabolism could probably play a role in MS more as an environmental factor rather than as a genetic factor. Our study also supports the analysis of cases and unaffected individuals within families in order to determine the influence of genetic factors.

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“…It is important mentioning that VDR, the intracellular receptor of calcitriol, has been detected in neurons, astrocytes and oligodendrocytes highlighting the importance that both VDR and calcitriol can play on brain development [61,62]. Also, the presence of CYP27B1 in several cell types in brain including endothelial cells, microglia, neurons and astrocytes [63], suggests that calcitriol synthesis could be an in situ process in central nervous system.…”

Section: The Beneficial Role Of Calcitriol In Neurodegenerative Diseamentioning

confidence: 99%

Calcitriol increases frataxin levels and restores altered markers in cell models of Friedreich Ataxia

Britti¹,

Delaspre²,

Medina-Carbonero³

et al. 2020

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Friedreich Ataxia (FA) is a neurodegenerative disease caused by the deficiency of frataxin, a mitochondrial protein. In primary cultures of dorsal root ganglia neurons, we showed that frataxin depletion resulted in decreased levels of the mitochondrial calcium exchanger NCLX, neurite degeneration and apoptotic cell death. Here we describe that frataxin-deficient dorsal root ganglia neurons display low levels of ferredoxin 1, a mitochondrial Fe/S cluster-containing protein that interacts with frataxin and, interestingly, is essential for the synthesis of calcitriol, the active form of vitamin D. We provide data that calcitriol supplementation, used at nanomolar concentrations, is able to reverse the molecular and cellular markers altered in DRG neurons. Calcitriol is able to recover both ferredoxin 1 and NCLX levels and restores mitochondrial membrane potential. Accordingly, apoptotic markers and neurite degeneration are reduced resulting in cell survival recovery with calcitriol supplementation. All these beneficial effects would be explained by the finding that calcitriol is able to increase the mature frataxin levels in both, frataxin-deficient DRG neurons and cardiomyocytes;remarkably, this increase also occurs in lymphoblastoid cell lines derived from FA patients. In conclusion, these results provide molecular bases to consider calcitriol for an easy and affordable therapeutic approach for FA patients.

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

Cited by 91 publications

References 25 publications

Genetic, environmental and biomarker considerations delineating the regulatory effects of vitamin D on central nervous system function

Genetic, environmental and biomarker considerations delineating the regulatory effects of vitamin D on central nervous system function

Exonic variants of genes related to the vitamin D signaling pathway in the families of familial multiple sclerosis using whole‐exome next generation sequencing

Calcitriol increases frataxin levels and restores altered markers in cell models of Friedreich Ataxia

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