Administration of vitamin D 3 induces CNPase and myelin oligodendrocyte glycoprotein expression in the cerebral cortex of the murine model of cuprizone-induced demyelination

Abstract

A b s t r a c t In the central nervous system (CNS) the main proteins of myelin are proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and CNPase. Myelin oligodendrocyte glycoprotein is a minor component of the myelin sheath, but is an important autoantigen linked to the pathogenesis of multiple sclerosis (MS). CNPase is expressed exclusively by oligodendrocytes in the CNS, and the appearance of CNPase seems to be one of the earliest events of oligodendrocyte differentiation and myelination. In this study the effects of vitamin D on total protein concentration, CNPase and MOG expression in the cerebral cortex of the murine model of cuprizone-induced demyelination was investigated. The mice were treated by cuprizone for five weeks in order to induce demyelination. The mice were then divided into 3 groups. The first group was injected intraperitoneally (IP) with vitamin D diluted in olive oil in the amount of 5 µg/kg/daily body weight. The second group (SHAM) was injected IP with olive oil and the third group was left without any injection as the control group (n = 11 for each group). After five weeks the mice were killed and the cerebral cortex was collected and the expression of CNPase and MOG was studied by Western blot. Total protein concentration in the vitamin D injected, SHAM and control groups were 0.918 ± 0.003, 0917 ± 0.004 and 0.916 ± 0.004 g/l, respectively (p > 0.05

Clemastine improves hypomyelination in rats with hypoxic–ischemic brain injury by reducing microglia-derived IL-1β via P38 signaling pathway

“…The present results showed that the expression levels of IL-1β and NLRP3 were decreased by clemastine (H1 receptor antagonist), but the expression of HH1R was unaffected and localized in the microglia. The OPCs include NG2 and PDGFR-α cells, which differentiate progressively in a multiprocess morphology and sequentially bind to anti-CNPase and anti-MBP antibodies [26][27][28]. Through differentiation and maturation, OPCs migrate to myelinated target axons to form myelin.…”

Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications

“… 34 , 159–162 , 266 Indeed, animals suffering from neurodegeneration showed increased expression of MBP, MOG and PLP upon cholecalciferol or calcitriol treatment compared with vehicle control. 159 , 160 , 266 , 267 Similarly, calcitriol treatment reduced OPC proliferation and lead to higher oligodendrocyte differentiation with consequent increase in MBP production in vitro . 133 , 266 In addition, rats suffering from ethidium–bromide induced demyelination showed decreased caspase-3 activation in the CNS when treated with calcitriol, suggesting also a beneficial effect of VitD on oligodendrocyte apoptosis in multiple sclerosis.…”

Oligodendrocytes in the aging brain

“…Similar nutrient mixtures or single nutrients may therefore be beneficial in supporting white matter in aging through provision of precursors and cofactors for myelin membrane synthesis. Many other nutrients have also shown beneficial effects on white matter protection in the context of damage or demyelination, including sphingomyelin (191), vitamins K and D (192)(193)(194), and taurine (195). While the benefit of such nutrient support in the non-pathological aging brain remains hypothetical, there is strong evidence that nutritional interventions can be beneficial in the context of white matter repair following injury and demyelination, and in protecting cognitive function in pathologies associated with white matter, therefore their utility in promoting healthy aging through oligodendrocyte support warrants further research.…”