Neurodegeneration
Medical Studies on Melatonin – Neurodegeneration
Melatonin also plays a key role in neuroprotection, because disruptions of the day/night cycle often have consequences for mental health. This has been proven on multiple occasions by studies. What’s more, the severity and course of diseases such as Alzheimer’s and Parkinson’s can be improved by melatonin.
Depression
Studies have observed that persons suffering from depression exhibit changes in their melatonin secretion and thus also their sleep/wake cycle. How we sleep is therefore also considered to be an important biomarker in the diagnosis, prevention and treatment of depression. By normalising these melatonin disorders, behaviour changes can be improved and depression mitigated.
Alzheimer’s and Parkinson’s disease
Low melatonin values, which are exhibited through daytime tiredness and nocturnal activity, are demonstrable in many Alzheimer’s and also Parkinson’s patients. Studies have been able to demonstrate that melatonin supplements administered for both of these diseases resulted in a significant improvement in symptoms, especially in the early stages of the disease.
Melatonin has a preventative effect
Melatonin has also been used to reduce oxidative stress in the brain and to reduce – or sometimes even prevent – the loss of nerve cells and damage to the brain. Melatonin is therefore primarily a preventative measure against Alzheimer’s and Parkinson’s disease. Studies are still under way to determine if it can be used in a curative capacity.
Medical Studies on Melatonin – Neurodegeneration
Association between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorder
Alterations in tryptophan and serotonin have been implicated in various mental disorders; but studies are limited on child neurodevelopmental disabilities such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD).
Melatonin ameliorates Parkinson’s disease via regulating microglia polarization in a RORα-dependent pathway
An important pathophysiological component of Parkinson's Disease (PD) is circadian rhythm disorder, closely related to a decrease in circulated melatonin (MLT) level. It has been reported recently that retinoic acid-associated orphan nuclear receptor (RORα), for the potentiallyendogenous ligand MLT, plays an important role in various diseases.
Biological correlates of altered circadian rhythms, autonomic functions and sleep problems in autism spectrum disorder
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by a complex and multifaceted neurobehavioral syndrome. In the last decades, several studies highlighted an increased prevalence of sleep problems in ASD, which would be associated with autonomic system and circadian rhythm disruption.
Melatonin ameliorates tau-related pathology via the miR-504-3p and CDK5 axis in Alzheimer’s disease
Intracellular accumulation of the microtubule-associated protein tau and its hyperphosphorylated forms is a key neuropathological feature of Alzheimer's disease (AD). Melatonin has been shown to prevent tau hyperphosphorylation in cellular and animal models. However, the molecular mechanisms by which melatonin attenuates tau hyperphosphorylation and tau-related pathologies are not fully understood.
Melatonin synthesized by activated microglia orchestrates the progression of microglia from a pro-inflammatory to a recovery/repair phenotype
Microglia, the sentinels of the central nervous system, are responsible for the surveillance and the innate defense against pathogen or danger/damage-associated molecular patterns. The response is fine-tuned to restrain pro-inflammatory responses, preserving neighboring cells. At the injured area, microglia temporarily shift to a pro-inflammatory phenotype (M1), followed by anti-inflammatory (M2) phenotypes. The duration and magnitude of the pro-inflammatory phase are finely regulated to avoid unnecessary loss of brain tissue.
The effect of melatonin on reduction in the need for sedative agents and duration of mechanical ventilation in traumatic intracranial hemorrhage patients: a randomized controlled trial
This study aimed to determine the effect of exogenous melatonin on the number of sedative drugs and the duration of mechanical ventilation in traumatic intracranial hemorrhage patients in ICU.
Melatonin-A Potent Therapeutic for Stroke and Stroke-Related Dementia
Secreted by the pineal gland to regulate the circadian rhythm, melatonin is a powerful antioxidant that has been used to combat oxidative stress in the central nervous system.
Dietary Melatonin Therapy Alleviates the Lamina Cribrosa Damages in Patients With Mild Cognitive Impairments: A Double-Blinded, Randomized Controlled Study.
Alzheimer's disease (AD) is a degenerative disease that is characterized by massive neuron devastations in the hippocampus and cortex. Mild cognitive impairment (MCI) is the transitory stage between normality and AD dementia. This study aimed to investigate the melatonin induced effects on the lamina cribrosa thickness (LCT) of patients with MCI.
The Effects of Melatonin Supplementation on Parameters of Mental Health, Glycemic Control, Markers of Cardiometabolic Risk, and Oxidative Stress in Diabetic Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.
This study evaluated the effects of melatonin supplementation on parameters of mental health, glycemic control, markers of cardiometabolic risk, and oxidative stress in diabetic hemodialysis (HD) patients.
Chronotype, circadian rhythms and mood.
Growing evidence shows a link between mood and chronotype. The majority of studies measure chronotype as a preference for morning/evening activities, rather than actual sleep behaviour (i.e. midsleep) or biological markers of sleep timing (e.g. dim light melatonin onset).
Clinical Impact of Melatonin on Breast Cancer Patients Undergoing Chemotherapy; Effects on Cognition, Sleep and Depressive Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial.
This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment.
Virtual discovery of melatonin receptor ligands to modulate circadian rhythms.
The neuromodulator melatonin synchronizes circadian rhythms and related physiological functions via actions at two G protein-coupled receptors: MT1 and MT2.
Daytime melatonin levels in saliva are associated with inflammatory markers and anxiety disorders.
The bidirectional interaction between melatonin and the immune system has largely gone unexplored in a clinical context and especially in a psychiatric population. This study explored the association between melatonin during the day and inflammatory cytokines in young adult patients seeking psychiatric care.
Melatonin and Parkinson Disease: Current Status and Future Perspectives for Molecular Mechanisms.
Parkinson disease (PD) is a chronic and neurodegenerative disease with motor and nonmotor symptoms. Multiple pathways are involved in the pathophysiology of PD, including apoptosis, autophagy, oxidative stress, inflammation, α-synuclein aggregation, and changes in the neurotransmitters.
New awakenings: current understanding of sleep dysfunction and its treatment in Parkinson’s disease.
The non-motor features of Parkinson's disease (PD) are increasingly being recognised. This review deals with the spectrum of sleep disorders associated with PD, which have a multifactorial aetiology and can significantly have an impact on the quality of life of patients and their carers.
Impact of Sleep Disorder as a Risk Factor for Dementia in Men and Women.
Sleep is an essential physiological process, especially for proper brain function through the formation of new pathways and processing information and cognition. Therefore, when sleep is insufficient, this can result in pathophysiologic conditions.
Poor sleep quality associates with self-reported psychiatric and cardiometabolic symptoms independently of sleep timing patterns in a large sample of rural and urban workers.
Poor sleep associates with mental and cardiometabolic pathological outcomes. The participation of sleep timing features in the pathways by which this relationship occurs is not clear.
The effect of melatonin on depressive symptoms and anxiety in patients after acute coronary syndrome: The MEDACIS randomized clinical trial.
Depression following acute coronary syndrome is prevalent and associated with increased mortality and morbidity. Melatonin may function as a primary prophylactic antidepressant substance and alleviate depressive symptoms. The study was undertaken to determine if melatonin administered following an acute coronary syndrome (ACS) could prevent development of depression.
Circadian insights into the biology of depression: Symptoms, treatments and animal models.
In depression, symptoms range from loss of motivation and energy to suicidal thoughts. Moreover, in depression alterations might be also observed in the sleep-wake cycle and in the daily rhythms of hormonal (e.g., cortisol, melatonin) secretion.
The Effects of Melatonin on the Descending Pain Inhibitory System and Neural Plasticity Markers in Breast Cancer Patients Receiving Chemotherapy: Randomized, Double-Blinded, Placebo-Controlled Trial.
Adjuvant chemotherapy for breast cancer (ACBC) has been associated with fatigue, pain, depressive symptoms, and disturbed sleep. And, previous studies in non-cancer patients showed that melatonin could improve the descending pain modulatory system (DPMS).
The Neuroprotective Effects of Melatonin: Possible Role in the Pathophysiology of Neuropsychiatric Disease.
Melatonin is a hormone that is secreted by the pineal gland. To date, melatonin is known to regulate the sleep cycle by controlling the circadian rhythm. However, recent advances in neuroscience and molecular biology have led to the discovery of new actions and effects of melatonin.
Advanced melatonin onset relative to sleep in women with unmedicated major depressive disorder.
Studies on circadian timing in depression have produced variable results, with some investigations suggesting phase advances and others phase delays. This variability may be attributable to differences in participant diagnosis, medication use, and methodology between studies.
Effects of light on human circadian rhythms, sleep and mood.
Humans live in a 24-hour environment, in which light and darkness follow a diurnal pattern. Our circadian pacemaker, the suprachiasmatic nuclei (SCN) in the hypothalamus, is entrained to the 24-hour solar day via a pathway from the retina and synchronises our internal biological rhythms.
Healthier rhythm, healthier brain? Integrity of circadian melatonin and temperature rhythms relates to the clinical state of brain-injured patients.
Healthy circadian rhythmicity has been suggested to relate to a better state of brain-injured patients and to support the emergence of consciousness in patient groups characterized by a relative instability thereof such as patients with disorders of consciousness (DOC).
Pineal gland abnormality in major depressive disorder.
Patients with major depressive disorder (MDD) often have circadian rhythm alteration and sleep disturbance. The pineal gland regulates the circadian rhythm and sleep by the secretion of melatonin neurohormone. However, the relationship between pineal abnormality and MDD remains elusive.
Melatonin: Clinical Perspectives in Neurodegeneration.
Prevention of neurodegenerative diseases is presently a major goal for our Society and melatonin, an unusual phylogenetically conserved molecule present in all aerobic organisms, merits consideration in this respect.
New Insights Into the Circadian Rhythm and Its Related Diseases.
Circadian rhythms (CR) are a series of endogenous autonomous oscillators generated by the molecular circadian clock which acting on coordinating internal time with the external environment in a 24-h daily cycle.
Melatonin MT1 receptor as a novel target in neuropsychopharmacology: MT1 ligands, pathophysiological and therapeutic implications, and perspectives.
Melatonin (MLT), a neuromodulator mainly acting through two G-protein coupled receptors MT1 and MT2, regulates many brain functions, including circadian rhythms, mood, pain and sleep. MLT and non-selective MT1/MT2 receptor agonists are clinically used in neuropsychiatric and/or sleep disorders.
Insomnia as a predictor of mental disorders: A systematic review and meta-analysis.
Previous research has identified insomnia as a predictor for the onset of depression. The aim of this meta-analysis is to investigate whether insomnia also predicts the onset of other mental disorders.
Melatonin is a biomarker of circadian dysregulation and is correlated with major depression and fibromyalgia symptom severity.
This study compared urinary 6-sulfatoxymelatonin (aMT6s) over 24 hours among fibromyalgia (FM), major depression disorder (MDD), and healthy control (HC) groups, and examined whether rhythm is correlated with depressive symptoms. To answer this question we compared the rhythm of urinary aMT6s secretion among each group in four time series: morning (06:00-12:00 hours), afternoon (12:00-18:00 hours), evening (18:00-24:00 hours), and night (24:00-06:00 hours). In the FM subjects, we assessed if the rhythm of urinary aMT6s secretion is associated with pain severity, sleep quality, number of trigger points (NTPs), and the pain pressure threshold (PPT).
Clinical uses of melatonin: evaluation of human trials.
During the last 20 years, numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine. The objective of this article is to review, in depth, the science regarding clinical trials performed to date.
Add-on melatonin improves sleep behavior in children with epilepsy: randomized, double-blind, placebo-controlled trial.
This double-blind, randomized, placebo-controlled study in epileptic children, aged 3 to 12 years, evaluated the effect of add-on melatonin on the sleep behavior of these children on sodium valproate monotherapy using a parental questionnaire.
Double blind study of melatonin effects on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type dementia.
Previously, we reported that morning bright light therapy improved sleep time and cognitive function in Alzheimer type of dementia.
Melatonin in epilepsy: first results of replacement therapy and first clinical results.
At a single evening dose of 5-10 mg, melatonin (MLT), the pineal gland hormone, can exert a positive effect on the frequency of epileptic attacks in children with sleep disturbances of various etiologies.