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Study of Melatonin in Neural Development
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Study of Melatonin in Neural Development

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (20 June 2022) | Viewed by 19722

Special Issue Editor

Dr. Gloria Benítez-King

E-Mail Website
Guest Editor
Instituto Nacional de Psiquiatría Ramon de la Fuente, Mexico City, Mexico
Interests: melatonin; olfactory neuronal precursors; cytoskeleton; neurodevelopment; schizophrenia; Alzheimer’s disease

Special Issue Information

Dear Colleagues,

Melatonin is a phylogenetically ancient molecule. It is present in almost all organisms, from bacteria to humans. It is synthesized in the pineal gland and in other types of cells and can also be exogenously administered. In the brain, this indolamine produces pleiotropic effects and synchronizes the body’s circadian rhythms. It acts as an anti-oxidant and as an immuno-modulator and ameliorates inflammatory cytokine release in cells and in animal models of oxidative injury. Additionally, the highest levels in the cell are found in mitochondria after exogenous administration, and it prevents mitochondrial dysfunction, energy failure, and apoptosis.

Melatonin regulates the neuronal cytoskeleton through melatonin receptor stimulation and by direct intracellular interaction with calmodulin and protein kinase C. The cytoskeletal structure plays a key role in neural development, a complex process by which new neurons are formed and integrated to the preexistent brain circuitry. Among them, it is worth noting that neurodevelopment includes neurogenesis, axogenesis, dendritogenesis, and synaptogenesis and that, nowadays, it is consider that neurodevelopment enhancers constitute a new alternative for the treatment of neuropsychiatric diseases. This Special Issue mainly collects evidence on the stimulatory effects of melatonin on neurodevelopment in the adult brain, as well as the signaling transduction pathways involved. In addition, we welcome evidence about relevant effects of melatonin related to neurodevelopment in bipolar disorder, schizophrenia, Alzheimer's disease, and major depression, as well as its possible therapeutic implications.

Dr. Gloria Benítez-King
Guest Editor

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Keywords

  • melatonin
  • olfactory neuronal precursors
  • calmodulin
  • AKT
  • melatonin receptors

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Published Papers (5 papers)

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Research

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15 pages, 3346 KiB  
Article
Antidepressant Low Doses of Ketamine and Melatonin in Combination Produce Additive Neurogenesis in Human Olfactory Neuronal Precursors
by Rosa Estrada-Reyes, Daniel B. Quero-Chávez, Salvador Alarcón-Elizalde, Montserrat G. Cercós, Citlali Trueta, Luis A. Constantino-Jonapa, Julián Oikawa-Sala, Jesús Argueta, Ricardo Cruz-Garduño, Margarita L. Dubocovich and Gloria A. Benítez-King
Molecules 2022, 27(17), 5650; https://doi.org/10.3390/molecules27175650 - 1 Sep 2022
Cited by 5 | Viewed by 3395
Abstract
Melatonin (MEL), an indolamine with diverse functions in the brain, has been shown to produce antidepressant-like effects, presumably through stimulating neurogenesis. We recently showed that the combination of MEL with ketamine (KET), an NMDA receptor antagonist, has robust antidepressant-like effects in mice, at [...] Read more.
Melatonin (MEL), an indolamine with diverse functions in the brain, has been shown to produce antidepressant-like effects, presumably through stimulating neurogenesis. We recently showed that the combination of MEL with ketamine (KET), an NMDA receptor antagonist, has robust antidepressant-like effects in mice, at doses that, by themselves, are non-effective and have no adverse effects. Here, we show that the KET/MEL combination increases neurogenesis in a clone derived from human olfactory neuronal precursors, a translational pre-clinical model for effects in the human CNS. Neurogenesis was assessed by the formation of cell clusters > 50 µm in diameter, positively stained for nestin, doublecortin, BrdU and Ki67, markers of progenitor cells, neurogenesis, and proliferation. FGF, EGF and BDNF growth factors increased the number of cell clusters in cultured, cloned ONPs. Similarly, KET or MEL increased the number of clusters in a dose-dependent manner. The KET/MEL combination further increased the formation of clusters, with a maximal effect obtained after a triple administration schedule. Our results show that the combination of KET/MEL, at subeffective doses that do not produce adverse effects, stimulate neurogenesis in human neuronal precursors. Moreover, the mechanism by which the combination elicits neurogenesis is meditated by melatonin receptors, CaM Kinase II and CaM antagonism. This could have clinical advantages for the fast treatment of depression. Full article
(This article belongs to the Special Issue Study of Melatonin in Neural Development)
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17 pages, 5442 KiB  
Article
Chronic Treatment with Melatonin Improves Hippocampal Neurogenesis in the Aged Brain and Under Neurodegeneration
by Cristina Cachán-Vega, Ignacio Vega-Naredo, Yaiza Potes, Juan Carlos Bermejo-Millo, Adrian Rubio-González, Claudia García-González, Eduardo Antuña, Manuel Bermúdez, José Gutiérrez-Rodríguez, José Antonio Boga, Ana Coto-Montes and Beatriz Caballero
Molecules 2022, 27(17), 5543; https://doi.org/10.3390/molecules27175543 - 29 Aug 2022
Cited by 8 | Viewed by 2773
Abstract
Adult hippocampal neurogenesis is altered during aging and under different neuropsychiatric and neurodegenerative diseases. Melatonin shows neurogenic and neuroprotective properties during aging and neuropathological conditions. In this study, we evaluated the effects of chronic treatment with melatonin on different markers of neurodegeneration and [...] Read more.
Adult hippocampal neurogenesis is altered during aging and under different neuropsychiatric and neurodegenerative diseases. Melatonin shows neurogenic and neuroprotective properties during aging and neuropathological conditions. In this study, we evaluated the effects of chronic treatment with melatonin on different markers of neurodegeneration and hippocampal neurogenesis using immunohistochemistry in the aged and neurodegenerative brains of SAMP8 mice, which is an animal model of accelerated senescence that mimics aging-related Alzheimer’s pathology. Neurodegenerative processes observed in the brains of aged SAMP8 mice at 10 months of age include the presence of damaged neurons, disorganization in the layers of the brain cortex, alterations in neural processes and the length of neuronal prolongations and β-amyloid accumulation in the cortex and hippocampus. This neurodegeneration may be associated with neurogenic responses in the hippocampal dentate gyrus of these mice, since we observed a neurogenic niche of neural stem and progenitor/precursors cells in the hippocampus of SAMP8 mice. However, hippocampal neurogenesis seems to be compromised due to alterations in the cell survival, migration and/or neuronal maturation of neural precursor cells due to the neurodegeneration levels in these mice. Chronic treatment with melatonin for 9 months decreased these neurodegenerative processes and the neurodegeneration-induced neurogenic response. Noticeably, melatonin also induced recovery in the functionality of adult hippocampal neurogenesis in aged SAMP8 mice. Full article
(This article belongs to the Special Issue Study of Melatonin in Neural Development)
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13 pages, 1115 KiB  
Article
Beneficial Effect of Melatonin Alone or in Combination with Glatiramer Acetate and Interferon β-1b on Experimental Autoimmune Encephalomyelitis
by Genaro Gabriel Ortíz, Ana Laura Briones-Torres, Gloria Benitez-King, Luis Javier González-Ortíz, Claudia Verónica Palacios-Magaña and Fermín Paul Pacheco-Moisés
Molecules 2022, 27(13), 4217; https://doi.org/10.3390/molecules27134217 - 30 Jun 2022
Cited by 3 | Viewed by 1727
Abstract
Experimental autoimmune encephalomyelitis (EAE) is a relevant animal model of multiple sclerosis (MS). Oxidative stress and chronic inflammation play a major role in the pathogenesis of MS and EAE. Melatonin, a neurohormone, has potent anti-inflammatory properties. The aim of our study was to [...] Read more.
Experimental autoimmune encephalomyelitis (EAE) is a relevant animal model of multiple sclerosis (MS). Oxidative stress and chronic inflammation play a major role in the pathogenesis of MS and EAE. Melatonin, a neurohormone, has potent anti-inflammatory properties. The aim of our study was to assess the therapeutic properties of melatonin alone or in combination with interferon β-1b (IFNβ-1b) or glatiramer acetate (GA) on EAE. EAE was induced in male Sprague-Dawley rats with an intraperitoneal injection of a homogenate of spinal cord and pig brain. At day 10 post immunization, rats were euthanized, and their brains were immediately excised and processed to measure oxidative stress markers and membrane fluidity. In addition, proinflammatory cytokines were quantified in plasma. Melatonin alone or in combination with GA and IFNβ-1b inhibited the disease process of EAE and the synthesis of proinflammatory cytokines, caused a significant decrement in oxidative stress markers, and preserved the membrane fluidity in the motor cortex, midbrain, and spinal cord. The cumulative index score was significantly reduced in EAE rats treated with melatonin alone or in combination with GA and IFNβ-1b. In conclusion, our findings provide preclinical evidence for the use of melatonin as an adjuvant therapeutic treatment for MS. Full article
(This article belongs to the Special Issue Study of Melatonin in Neural Development)
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Review

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16 pages, 2292 KiB  
Review
Melatonin: A Neurotrophic Factor?
by Armida Miranda-Riestra, Rosa Estrada-Reyes, Erandis D. Torres-Sanchez, Silvia Carreño-García, Genaro Gabriel Ortiz and Gloria Benítez-King
Molecules 2022, 27(22), 7742; https://doi.org/10.3390/molecules27227742 - 10 Nov 2022
Cited by 17 | Viewed by 5724
Abstract
Melatonin, N-acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly depends on the endogenous circadian clock located in the suprachiasmatic nucleus and the retina’s exposure to different light intensities. Among [...] Read more.
Melatonin, N-acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly depends on the endogenous circadian clock located in the suprachiasmatic nucleus and the retina’s exposure to different light intensities. Among its most studied functions are the regulation of the waking-sleep rhythm and body temperature. Furthermore, melatonin has pleiotropic actions, which affect, for instance, the modulation of the immune and the cardiovascular systems, as well as the neuroprotection achieved by scavenging free radicals. Recent research has supported that melatonin contributes to neuronal survival, proliferation, and differentiation, such as dendritogenesis and axogenesis, and its processes are similar to those caused by Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5. Furthermore, this indolamine has apoptotic and anti-inflammatory actions in specific brain regions akin to those exerted by neurotrophic factors. This review presents evidence suggesting melatonin’s role as a neurotrophic factor, describes the signaling pathways involved in these processes, and, lastly, highlights the therapeutic implications involved. Full article
(This article belongs to the Special Issue Study of Melatonin in Neural Development)
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16 pages, 2502 KiB  
Review
Psycho-Neuro-Endocrine-Immunology: A Role for Melatonin in This New Paradigm
by Oscar K. Bitzer-Quintero, Genaro G. Ortiz, Socorro Jaramillo-Bueno, Elsy J. Ramos-González, María G. Márquez-Rosales, Daniela L. C. Delgado-Lara, Erandis D. Torres-Sánchez, Aldo R. Tejeda-Martínez and Javier Ramirez-Jirano
Molecules 2022, 27(15), 4888; https://doi.org/10.3390/molecules27154888 - 30 Jul 2022
Cited by 7 | Viewed by 5262
Abstract
Psychoneuroendocrinoimmunology is the area of study of the intimate relationship between immune, physical, emotional, and psychological aspects. This new way of studying the human body and its diseases was initiated in the last century’s first decades. However, the molecules that participate in the [...] Read more.
Psychoneuroendocrinoimmunology is the area of study of the intimate relationship between immune, physical, emotional, and psychological aspects. This new way of studying the human body and its diseases was initiated in the last century’s first decades. However, the molecules that participate in the communication between the immune, endocrine, and neurological systems are still being discovered. This paper aims to describe the development of psychoneuroendocrinoimmunology, its scopes, limitations in actual medicine, and the extent of melatonin within it. Full article
(This article belongs to the Special Issue Study of Melatonin in Neural Development)
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