Vitamina D y remielinización en la esclerosis múltiple

Oreja‐Guevara, Celia; Matías‐Guiu, Jordi A.; Gómez‐Pinedo, Ulises

doi:10.1016/j.nrl.2016.05.001

“…In the development of MS, CD4 T lymphocytes (or T helper lymphocytes, including Th1, Th2, Th17 subsets) play a crucial role in the activation of myelin-specific Th1 and Th17 cells, which drives the inflammation within the central nervous system [ 36 , 37 ]. Second, MS is characterized by progressive demyelination, vitamin D is deemed to have a role in the myelination and remyelination processes [ 38 – 41 ], and finally, 80% of MS-associated genes are enriched for VDREs in their promoter region and consequently, and they are regulated by vitamin D [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms CYP2R1 rs10766197 and CYP27B1 rs10877012 in Multiple Sclerosis: A Case-Control Study

Martínez-Hernández

¹

,

Pérez-Guerrero

²

,

Macías-Islas

³

et al. 2021

Journal of Immunology Research

6

1

0

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Background. Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D [25(OH) vitamin D] levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. Results. Serum 25(OH) vitamin D levels were lower in MS patients than in controls ( p = 0.009 ). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression ( p = 0.88 ). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls ( p = 0.05 ). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 ( p = 0.65 ). In subanalysis, patients with GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls ( p = 0.03 ). No increased risk was observed in GT + TT genotypes of CYP27B1 rs10877012 ( p = 0.63 ). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. Conclusion. Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.

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“…Activated microglia may contribute to the immunopathogenesis of MS through several mechanisms that involve an increased secretion of proinflammatory cytokines, chemokines, free radicals, and glutamate [5]. The overexpression of those molecules can provide a hostile microenvironment that limits oligodendrocyte precursor cells (OPCs) migration and differentiation into myelinating oligodendrocytes and leads to ineffective remyelination at the advanced stages of the disease [24].…”

Section: Multiple Sclerosismentioning

confidence: 99%

Exosomes and Biomaterials: In Search of a New Therapeutic Strategy for Multiple Sclerosis

Ojeda-Hernández

¹

,

Hernández-Sapiéns²,

Reza-Zaldívar

³

et al. 2022

Life

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Current efforts to find novel treatments that counteract multiple sclerosis (MS) have pointed toward immunomodulation and remyelination. Currently, cell therapy has shown promising potential to achieve this purpose. However, disadvantages such as poor survival, differentiation, and integration into the target tissue have limited its application. A series of recent studies have focused on the cell secretome, showing it to provide the most benefits of cell therapy. Exosomes are a key component of the cell secretome, participating in the transfer of bioactive molecules. These nano-sized vesicles offer many therapeutical advantages, such as the capacity to cross the blood-brain barrier, an enrichable cargo, and a customizable membrane. Moreover, integrating of biomaterials into exosome therapy could lead to new tissue-specific therapeutic strategies. In this work, the use of exosomes and their integration with biomaterials is presented as a novel strategy in the treatment of MS.

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“…As a result, MS physicians routinely prescribe oral supplements of Vit D3 to increase and maintain Vit D levels in MS patients (Dörr et al, 2020 ). Previous studies suggest that Vit D3 plays a pivotal role in immunomodulatory in MS (Chiuso-Minicucci et al, 2015 ; Mimura et al, 2016 ) and remyelination through stimulating the differentiation of oligodendrocyte progenitor cells (OPC; de la Fuente et al, 2015 ; Matías-Guíu et al, 2018 ). In addition, Wergeland et al ( 2011 ) reported that administration of Vit D3 after 2 weeks of cuprizone (CPZ) withdrawal improved remyelination, and inhibited microglia/macrophage activation in the CPZ mouse model.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of combination vitamin D3 and siponimod on remyelination and modulate microglia activation in cuprizone mouse model of multiple sclerosis

Al-Otaibi

¹

,

Alghamdi²,

Alghamdi³

et al. 2023

Front. Behav. Neurosci.

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Stimulation of remyelination is critical for the treatment of multiple sclerosis (MS) to alleviate symptoms and protect the myelin sheath from further damage. The current study aimed to investigate the possible therapeutic effects of combining vitamin D3 (Vit D3) and siponimod (Sipo) on enhancing remyelination and modulating microglia phenotypes in the cuprizone (CPZ) demyelination mouse model. The study was divided into two stages; demyelination (first 5 weeks) and remyelination (last 4 weeks). In the first 5 weeks, 85 mice were randomly divided into two groups, control (n = 20, standard rodent chow) and CPZ (n = 65, 0.3% CPZ mixed with chow for 6 weeks, followed by 3 weeks of standard rodent chow). At week 5, the CPZ group was re-divided into four groups (n = 14) for remyelination stages; untreated CPZ (0.2 ml of CMC orally), CPZ+Vit D3 (800 IU/kg Vit D3 orally), CPZ+Sipo (1.5 mg/kg Sipo orally), and CPZ+Vit D3 (800 IU/kg Vit D3) + Sipo (1.5 mg/kg Sipo orally). Various behavioral tasks were performed to evaluate motor performance. Luxol Fast Blue (LFB) staining, the expression level of myelin basic protein (MBP), and M1/M2 microglia phenotype genes were assessed in the corpus callosum (CC). The results showed that the combination of Vit D3 and Sipo improved behavioral deficits, significantly promoted remyelination, and modulated expression levels of microglia phenotype genes in the CC at early and late remyelination stages. These results demonstrate for the first time that a combination of Vit D3 and Sipo can improve the remyelination process in the cuprizone (CPZ) mouse model by attenuating the M1 microglia phenotype. This may help to improve the treatment of MS patients.

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Vitamina D y remielinización en la esclerosis múltiple

Abstract: VD seems to play a role in the CNS and our hypothesis is that VD is involved in remyelination. Understanding the basic mechanisms of VD in myelination is necessary to manage multiple sclerosis patients with VD deficiency.

Cited by 29 publications

References 131 publications

Polymorphisms CYP2R1 rs10766197 and CYP27B1 rs10877012 in Multiple Sclerosis: A Case-Control Study

Polymorphisms CYP2R1 rs10766197 and CYP27B1 rs10877012 in Multiple Sclerosis: A Case-Control Study

Exosomes and Biomaterials: In Search of a New Therapeutic Strategy for Multiple Sclerosis

Therapeutic effect of combination vitamin D3 and siponimod on remyelination and modulate microglia activation in cuprizone mouse model of multiple sclerosis

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