ArticleFrontiers in pharmacology2019
Melatonin Therapy Modulates Cerebral Metabolism and Enhances Remyelination by Increasing PDK4 in a Mouse Model of Multiple Sclerosis.
Article in Frontiers in pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- The effects of melatonin supplementation on neurobehavioral outcomes and clinical severity in rodent models of multiple sclerosis; a systematic review and meta-analysis.Inflammopharmacology · 2024Pooled it
- Melatonin ameliorates astrogliosis and microgliosis in a cuprizone demyelinating mouse model.Biochemistry and biophysics reports · 2025Article
- Protective Activity of Melatonin Combinations and Melatonin-Based Hybrid Molecules in Neurodegenerative Diseases.Journal of pineal research · 2024Review
- New Perspectives on the Role and Therapeutic Potential of Melatonin in Cardiovascular Diseases.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Review
- Pineal gland volume loss in females with multiple sclerosis.Frontiers in neuroanatomy · 2024Article
- REDOX Balance in Oligodendrocytes Is Important for Zebrafish Visual System Regeneration.Antioxidants (Basel, Switzerland) · 2023Article
- Melatonin and vitamin D, two sides of the same coin, better to land on its edge to improve multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2023Review
- Influence of hormones in multiple sclerosis: focus on the most important hormones.Metabolic brain disease · 2023Review
- Inhibiting nighttime melatonin and boosting cortisol increase patrolling monocytes, phagocytosis, and myelination in a murine model of multiple sclerosis.Experimental & molecular medicine · 2023Article
- Reaction of different cell types of the brain on neurotoxin cuprizone and hormone melatonin treatment in young and aging mice.Frontiers in cellular neuroscience · 2023Article
- Mitochondria in innate immunity signaling and its therapeutic implications in autoimmune diseases.Frontiers in immunology · 2023Review
- The potential influence of melatonin on mitochondrial quality control: a review.Frontiers in pharmacology · 2023Review
- A Novel Role of Nogo Proteins: Regulating Macrophages in Inflammatory Disease.Cellular and molecular neurobiology · 2022Review
- Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action.Inflammopharmacology · 2022Review
- Melatonin ameliorates disease severity in a mouse model of multiple sclerosis by modulating the kynurenine pathway.Scientific reports · 2022Article
- Targeting Nrf2-Mediated Oxidative Stress Response in Traumatic Brain Injury: Therapeutic Perspectives of Phytochemicals.Oxidative medicine and cellular longevity · 2022Review
- PDK4 Inhibition Ameliorates Melatonin Therapy by Modulating Cerebral Metabolism and Remyelination in an EAE Demyelinating Mouse Model of Multiple Sclerosis.Frontiers in immunology · 2022Article
- Review
- Hormonal Regulation of Oligodendrogenesis I: Effects across the Lifespan.Biomolecules · 2021Review
- Immunometabolic Pathways and Its Therapeutic Implication in Autoimmune Diseases.Clinical reviews in allergy & immunology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic disturbances have been implicated in demyelinating diseases including multiple sclerosis (MS). Melatonin, a naturally occurring hormone, has emerged as a potent neuroprotective candidate to reduce myelin loss and improve MS outcomes. In this study, we evaluated the effect of melatonin, at both physiological and pharmacological doses, on oligodendrocytes metabolism in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Results showed that melatonin decreased neurological disability scores and enhanced remyelination, significantly increasing myelin protein levels including MBP, MOG, and MOBP. In addition, melatonin attenuated inflammation by reducing pro-inflammatory cytokines (IL-1β and TNF-α) and increasing anti-inflammatory cytokines (IL-4 and IL-10). Moreover, melatonin significantly increased brain concentrations of lactate, N-acetylaspartate (NAA), and 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR). Pyruvate dehydrogenase kinase-4 (PDK-4) mRNA and protein expression levels were also increased in melatonin-treated, compared to untreated EAE mice. However, melatonin significantly inhibited active and total pyruvate dehydrogenase complex (PDC), an enzyme under the control of PDK4. In summary, although PDC activity was reduced by melatonin, it caused a reduction in inflammatory mediators while stimulating oligodendrogenesis, suggesting that oligodendrocytes are forced to use an alternative pathway to synthesize fatty acids for remyelination. We propose that combining melatonin and PDK inhibitors may provide greater benefits for MS patients than the use of melatonin therapy alone.
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Registered trials
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