Melatonin Effects in Young and Aging Mice with the Toxic Cuprizone-Induced Demyelination

Labunets, I. F.; Rodnichenko, A. E.

doi:10.1134/s2079057020010105

Cited by 5 publications

(12 citation statements)

References 26 publications

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“…Each experimental group contained 10 animals. This work does not include a group of cuprizone-treated mice, which were injected with melatonin or rhFGF-2 only since these studies were published previously [12,15]. However, the common methodological approaches in the previous and present studies allow us to compare the effects of melatonin and rhFGF-2 when administered alone and in combination with hMMSCs.…”

Section: Methodsmentioning

confidence: 99%

“…The behavioral reactions in mice were studied in the "open field" test and rotarod test [12]. In the "open field" test we evaluated: horizontal locomotor, exploratory and emotional activity.…”

Section: Methodsmentioning

confidence: 99%

“…Factors of oxidative stress and antioxidant protection were determined, as described previously [12,20]. The malondialdehyde (MDA) content in brain homogenate was determined by colour intensity of the trimethine complex formed between thiobarbituric acid and MDA.…”

Section: Methodsmentioning

confidence: 99%

“…Anti-inflammatory properties of hMMSCs may be also important in their positive effects in cuprizone-treated mice. Thus, cuprizone led to imbalances in pro-and anti-inflammatory cytokines and activation of macroglia cells in the brain [1,12,20]. However, after the injection of hMMSCs to the animals with demyelinating pathology, a decrease in reactive gliosis in the brain and behavior improving were established [6,24].…”

Section: Influence Of Hmmscs Transplantation On the Behavior And Oxidative Stress In The Brain Of Cuprizone-treated Micementioning

confidence: 99%

“…Melatonin also exhibits neurotrophic, antioxidant, antiinflammatory, immunomodulatory and antiapoptotic properties [10,11]. Noteworthy, the melatonin production by the pineal gland is reduced in the animal multiple sclerosis models whereas the injections of this hormone have neuroprotective and remyelinating effects and improve the central nervous system (CNS) functioning [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Melatonin and fibroblast growth factor-2 potentiate the effects of human umbilical cord multipotent mesenchymal stromal cells in mice with cuprizone-induced demyelination

et al. 2021

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To study the influence of melatonin and recombinant human fibroblast growth factor (rhFGF-2) on human umbilical cord multipotent mesenchymal stromal cells (hMMSCs) effects at experimental demyelination. Methods. Adult mice were fed with neurotoxin cuprizone for 3 weeks. hMMSCs (5×10 5 cells) were injected on the 10th day of cuprizone diet. Injections of melatonin or rhFGF-2 were started on the 11th day of cuprizone diet. We used cell culture, flow cytometric, spectrophotometric and histological methods, "open field" and "rotarod" tests. Results. Under the cuprizone influence the motor-, emotional activities and muscle tone decreased. The malondialdehyde (MDA) content in brain increased while the activity of antioxidant enzymes decreased. After injection of hMMSCs the number of crossed squares and grooming activity increased while MDA content decreased. Melatonin and rhFGF-2 injections enhanced the effect of cells on grooming activity and increased the glutathione reductase activity. Melatonin also increased the number of boluses, muscle tone and glutathione peroxidase activity. Conclusion. Melatonin and rhFGF-2 improve the effect of hMMSCs in cuprizonetreated mice. The effects of hMMSCs and melatonin combination is greater than that with rhFGF-2.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Influence Of Hmmscs Transplantation On the Behavior And Oxidative Stress In The Brain Of Cuprizone-treated Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Melatonin and fibroblast growth factor-2 potentiate the effects of human umbilical cord multipotent mesenchymal stromal cells in mice with cuprizone-induced demyelination

et al. 2021

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Inhibiting nighttime melatonin and boosting cortisol increase patrolling monocytes, phagocytosis, and myelination in a murine model of multiple sclerosis

et al. 2023

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Conflicting results on melatonin synthesis in multiple sclerosis (MS) have been reported due to variabilities in patient lifestyles, which are not considered when supplementing melatonin. Since melatonin acts through its receptors, we identified melatonin receptors in oligodendrocytes (OLs) in the corpus callosum, where demyelination occurs; the subventricular zone, where neural stem/progenitor cells (NSPCs) are located; and the choroid plexus, which functions as a blood-cerebrospinal fluid barrier. Moreover, using chimeric mice, resident macrophages were found to express melatonin receptors, whereas bone marrow-derived macrophages lost this expression in the demyelinated brain. Next, we showed that cuprizone-fed mice, which is an MS model, tended to have increased melatonin levels. While we used different approaches to alter the circadian rhythm of melatonin and cortisol, only the constant light approach increased NSPC proliferation and differentiation to oligodendrocyte precursor cells (OPCs), OPCs maturation to OLs and recruitment to the site of demyelination, the number of patrolling monocytes, and phagocytosis. In contrast, constant darkness and exogenous melatonin exacerbated these events and amplified monocyte infiltration. Therefore, melatonin should not be considered a universal remedy, as is currently claimed. Our data emphasize the importance of monitoring melatonin/cortisol oscillations in each MS patient by considering diet and lifestyle to avoid melatonin overdose.

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Effects of Multipotent Mesenchymal Stromal Cells of the Human Umbilical Cord and Their Combination with Melatonin in Adult and Aging Mice with a Toxic Cuprizone Model of Demyelination

2021

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Melatonin Effects in Young and Aging Mice with the Toxic Cuprizone-Induced Demyelination

Cited by 5 publications

References 26 publications

Melatonin and fibroblast growth factor-2 potentiate the effects of human umbilical cord multipotent mesenchymal stromal cells in mice with cuprizone-induced demyelination

Melatonin and fibroblast growth factor-2 potentiate the effects of human umbilical cord multipotent mesenchymal stromal cells in mice with cuprizone-induced demyelination

Inhibiting nighttime melatonin and boosting cortisol increase patrolling monocytes, phagocytosis, and myelination in a murine model of multiple sclerosis

Effects of Multipotent Mesenchymal Stromal Cells of the Human Umbilical Cord and Their Combination with Melatonin in Adult and Aging Mice with a Toxic Cuprizone Model of Demyelination

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