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Frontiers in Physiology 2023A rhythmic expression of clock genes occurs within the cells of multiple organs and tissues throughout the body, termed "peripheral clocks." Peripheral clocks are... (Review)
Review
A rhythmic expression of clock genes occurs within the cells of multiple organs and tissues throughout the body, termed "peripheral clocks." Peripheral clocks are subject to entrainment by a multitude of factors, many of which are directly or indirectly controlled by the light-entrainable clock located in the suprachiasmatic nucleus of the hypothalamus. Peripheral clocks occur in the gastrointestinal tract, notably the epithelia whose functions include regulation of absorption, permeability, and secretion of hormones; and in the myenteric plexus, which is the intrinsic neural network principally responsible for the coordination of muscular activity in the gut. This review focuses on the physiological circadian variation of major colonic functions and their entraining mechanisms, including colonic motility, absorption, hormone secretion, permeability, and pain signalling. Pathophysiological states such as irritable bowel syndrome and ulcerative colitis and their interactions with circadian rhythmicity are also described. Finally, the classic circadian hormone melatonin is discussed, which is expressed in the gut in greater quantities than the pineal gland, and whose exogenous use has been of therapeutic interest in treating colonic pathophysiological states, including those exacerbated by chronic circadian disruption.
PubMed: 37711458
DOI: 10.3389/fphys.2023.1239278 -
Frontiers in Cell and Developmental... 2023Spinal cord injury (SCI) is a sudden onset of disruption to the spinal neural tissue, leading to loss of motor control and sensory function of the body. Oxidative stress... (Review)
Review
Spinal cord injury (SCI) is a sudden onset of disruption to the spinal neural tissue, leading to loss of motor control and sensory function of the body. Oxidative stress is considered a hallmark in SCI followed by a series of events, including inflammation and cellular apoptosis. Melatonin was originally discovered as a hormone produced by the pineal gland. The subcellular localization of melatonin has been identified in mitochondria, exhibiting specific onsite protection to excess mitochondrial reactive oxygen species and working as an antioxidant in diseases. The recent discovery regarding the molecular basis of ligand selectivity for melatonin receptors and the constant efforts on finding synthetic melatonin alternatives have drawn researchers' attention back to melatonin. This review outlines the application of melatonin in SCI, including 1) the relationship between the melatonin rhythm and SCI in clinic; 2) the neuroprotective role of melatonin in experimental traumatic and ischemia/reperfusion SCI, i.e., exhibiting anti-oxidative, anti-inflammatory, and anti-apoptosis effects, facilitating the integrity of the blood-spinal cord barrier, ameliorating edema, preventing neural death, reducing scar formation, and promoting axon regeneration and neuroplasticity; 3) protecting gut microbiota and peripheral organs; 4) synergizing with drugs, rehabilitation training, stem cell therapy, and biomedical material engineering; and 5) the potential side effects. This comprehensive review provides new insights on melatonin as a natural antioxidant therapy in facilitating rehabilitation in SCI.
PubMed: 37691830
DOI: 10.3389/fcell.2023.1218553 -
International Journal of Molecular... Aug 2023Melatonin is a hormone synthesized by the pineal gland with neuroprotective and neurodevelopmental effects. Also, melatonin acts as an antidepressant by modulating the...
Melatonin Prevents Depression but Not Anxiety-like Behavior Produced by the Chemotherapeutic Agent Temozolomide: Implication of Doublecortin Cells and Hilar Oligodendrocytes.
Melatonin is a hormone synthesized by the pineal gland with neuroprotective and neurodevelopmental effects. Also, melatonin acts as an antidepressant by modulating the generation of new neurons in the dentate gyrus of the hippocampus. The positive effects of melatonin on behavior and neural development may suggest it is used for reverting stress but also for the alterations produced by chemotherapeutic drugs influencing behavior and brain plasticity. In this sense, temozolomide, an alkylating/anti-proliferating agent used in treating brain cancer, is associated with decreased cognitive functions and depression. We hypothesized that melatonin might prevent the effects of temozolomide on depression- and anxiety-like behavior by modulating some aspects of the neurogenic process in adult Balb/C mice. Mice were treated with temozolomide (25 mg/kg) for three days of two weeks, followed by melatonin (8 mg/kg) for fourteen days. Temozolomide produced short- and long-term decrements in cell proliferation (Ki67-positive cells: 54.89% and 53.38%, respectively) and intermediate stages of the neurogenic process (doublecortin-positive cells: 68.23% and 50.08%, respectively). However, melatonin prevented the long-term effects of temozolomide with the increased number of doublecortin-positive cells (47.21%) and the immunoreactivity of 2' 3'-Cyclic-nucleotide-3 phosphodiesterase (CNPase: 82.66%), an enzyme expressed by mature oligodendrocytes, in the hilar portion of the dentate gyrus. The effects of melatonin in the temozolomide group occurred with decreased immobility in the forced swim test (45.55%) but not anxiety-like behavior. Thus, our results suggest that melatonin prevents the harmful effects of temozolomide by modulating doublecortin cells, hilar oligodendrocytes, and depression-like behavior tested in the forced swim test. Our study could point out melatonin's beneficial effects for counteracting temozolomide's side effects.
Topics: Animals; Mice; 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; Depression; Doublecortin Domain Proteins; Melatonin; Mice, Inbred BALB C; Neurons; Temozolomide
PubMed: 37686181
DOI: 10.3390/ijms241713376 -
Zhongguo Dang Dai Er Ke Za Zhi =... Aug 2023Neonatal hypoxic-ischemic encephalopathy (HIE) remains one of the leading causes of death and long-term neurodevelopmental disorders in full-term neonates, and there is... (Review)
Review
Neonatal hypoxic-ischemic encephalopathy (HIE) remains one of the leading causes of death and long-term neurodevelopmental disorders in full-term neonates, and there is currently no curative treatment. Therapeutic hypothermia is now a standard therapy for HIE in the neonatal intensive care unit, but its safety and efficacy in remote areas remains unclear. Melatonin is an indole endocrine hormone mainly produced by the pineal gland and it has the ability to easily penetrate the blood-brain barrier. Through receptor and non-receptor mechanisms, melatonin exerts anti-oxidative and anti-inflammatory effects and participates in the regulation of organelle function and the inhibition of cell death. Melatonin is considered one of the most promising drugs for the treatment of HIE based on its reliable safety profile and clinical/preclinical results. This article reviews the recent research on the use of melatonin in combination with therapeutic hypothermia for the treatment of neonatal HIE.
Topics: Infant, Newborn; Humans; Melatonin; Hypoxia-Ischemia, Brain; Hypothermia, Induced; Intensive Care Units, Neonatal
PubMed: 37668036
DOI: 10.7499/j.issn.1008-8830.2302099 -
Cureus Jul 2023Convergence-retraction nystagmus alongside behavioral changes can be rare manifestations of a potentially life-threatening midbrain lesion. After experiencing headaches...
Convergence-retraction nystagmus alongside behavioral changes can be rare manifestations of a potentially life-threatening midbrain lesion. After experiencing headaches for three months, a 13-year-old boy was diagnosed with depression due to exhibiting reduced speech, hypersomnia, and psychomotor slowing for three weeks. It was preceded by headache for three months. Examination revealed visual acuity of 6/6 bilaterally, convergence-retraction nystagmus worst on upgaze, limited bilateral ocular motility in upgaze, and light-near dissociation on pupil examination, all of which point towards Parinaud's syndrome. However, there was no lid retraction to suggest Collier's sign. Fundus examination revealed papilledema. Magnetic resonance imaging showed a large pineal mass extending to both thalami, dilated ventricles due to obstructive hydrocephalus, and cerebral edema. An urgent external ventricular drain was inserted, and biopsy revealed pineal gland germinoma. Chemotherapy and radiotherapy resulted in adequate tumor shrinkage. This case report highlights that subacute behavioral changes may mask a potentially life-threatening intracranial tumor, especially when associated with abnormal eye movement.
PubMed: 37637548
DOI: 10.7759/cureus.42497 -
Antioxidants (Basel, Switzerland) Aug 2023Melatonin is a hormone that regulates sleep-wake cycles and is mainly synthesized in the pineal gland from tryptophan after its conversion into serotonin. Under normal...
Melatonin is a hormone that regulates sleep-wake cycles and is mainly synthesized in the pineal gland from tryptophan after its conversion into serotonin. Under normal conditions, less than 5% of tryptophan is reserved for the synthesis of serotonin and melatonin. The remaining 95% is metabolized in the liver through the kynurenine pathway. Increased levels of proinflammatory cytokines and cortisol increase the metabolism of tryptophan through the kynurenine pathway and reduce its availability for the synthesis of melatonin and serotonin, which may cause alterations in mood and sleep. The standardized saffron extract (affron) has shown beneficial effects on mood and sleep disorders in humans, but the underlying mechanisms are not well understood. Thus, the aim of this work was to study the effects of affron supplementation on the kynurenine pathway and the synthesis of melatonin in rats. For this purpose, adult male Wistar rats were supplemented for 7 days with 150 mg/kg of affron or vehicle (2 mL/kg water) administered by gavage one hour before sleep. Affron supplementation reduced body weight gain and increased the circulating levels of melatonin, testosterone, and c-HDL. Moreover, animals supplemented with affron showed decreased serum levels of kynurenine, ET-1, and c-LDL. In the pineal gland, affron reduced expression and increased the expression of , the key enzyme for melatonin synthesis. In the liver, affron administration decreased the mRNA levels of the enzymes of the kynurenine pathway , , and , as well as the gene expression of and . Finally, rats treated with affron showed increased mRNA levels of the antioxidant enzymes , , , and , both in the liver and in the pineal gland. In conclusion, affron supplementation reduces kynurenine levels and promotes melatonin synthesis in rats, possibly through its antioxidant and anti-inflammatory effects, making this extract a possible alternative for the treatment and/or prevention of mood and sleep disorders.
PubMed: 37627614
DOI: 10.3390/antiox12081619 -
Animals : An Open Access Journal From... Aug 2023Imidacloprid (IMI) is an endogenous neonicotinoid insecticide widely used in agriculture and has attracted researchers' attention because of its risks to the environment...
Imidacloprid (IMI) is an endogenous neonicotinoid insecticide widely used in agriculture and has attracted researchers' attention because of its risks to the environment and human health. Melatonin (MT) is an antioxidant hormone produced by the pineal gland of the brain. Studies have shown that it has a variety of physiological functions and plays a crucial role in the development of animal germ cells and embryos. The potential protective effects of MT against oocyte damage caused by neonicotinoid pesticide toxicity remain unclear. In this study, we report the toxicity of IMI against, and its effects on the quality of, porcine oocytes and the protective effect of MT on IMI-exposed oocytes. The results show that IMI exposure adversely affected oocyte maturation, while MT supplementation ameliorated its toxic effects. Specifically, IMI exposure increased oxidative stress (OS), endoplasmic reticulum stress (ERS), and apoptosis, which may affect polar body expulsion rates and blastocyst formation. Also, IMI exposure reduced oocyte cleavage rates and the number of cells in blastocysts. However, all of these toxic effects can be restored after a melatonin supplementation treatment. In conclusion, these results suggest that melatonin has a protective effect on IMI-induced defects during porcine oocyte maturation.
PubMed: 37627386
DOI: 10.3390/ani13162596 -
Biomedicine & Pharmacotherapy =... Oct 2023Septic cardiomyopathy (SCM) is a common complication of sepsis contributing to high mortality rates. Its pathophysiology involves complex factors, including inflammatory... (Review)
Review
Septic cardiomyopathy (SCM) is a common complication of sepsis contributing to high mortality rates. Its pathophysiology involves complex factors, including inflammatory cytokines, mitochondrial dysfunction, oxidative stress, and immune dysregulation. Despite extensive research, no effective pharmacological agent has been established for sepsis-induced cardiomyopathy. Melatonin, a hormone with diverse functions in the body, has emerged as a potential agent for SCM through its anti-oxidant, anti-inflammatory, anti-apoptotic, and cardioprotective roles. Through various molecular levels of its mechanism of action, it counterattacks the adverse event of sepsis. Experimental studies have mentioned that melatonin protects against many cardiovascular diseases and exerts preventive effects on SCM. Moreover, melatonin has been investigated in combination with other drugs such as antibiotics, resveratrol, and anti-oxidants showing synergistic effects in reducing inflammation, anti-oxidant, and improving cardiac function. While preclinical studies have demonstrated positive results, clinical trials are required to establish the optimal dosage, route of administration, and treatment duration for melatonin in SCM. Its safety profile, low toxicity, and natural occurrence in the human body provide a favorable basis for its clinical use. This review aims to provide an overview of the current evidence of the use of melatonin in sepsis-induced cardiomyopathy (SICM). Melatonin appears to be promising as a possible treatment for sepsis-induced cardiomyopathy and demands further investigation.
Topics: Humans; Melatonin; Antioxidants; Cardiomyopathies; Cardiovascular Diseases; Sepsis
PubMed: 37619482
DOI: 10.1016/j.biopha.2023.115305