Neurodegeneration

Medical Studies on Melatonin – Neurodegeneration

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

Melatonin ameliorates Parkinson’s disease via regulating microglia polarization in a RORα-dependent pathway

2022-07 Li J, Liu H, Wang X, Xia Y, Huang J, Wang T, Lin Z, Xiong N

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

2022-05 Dell'Osso L, Massoni L, Battaglini S, Cremone IM, Carmassi C, Carpita B

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

2022-05 Chen D, Lan G, Li R, Mei Y, Shui X, Gu X, Wang L, Zhang T, Gan CL, Xia Y, Hu L, Tian Y, Zhang M, Lee TH

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

2022-03 Souza ES, Santo AA, Ribeiro-Paz EE, Córdoba-Moreno M, Trevisan IL, Caldeira W, Muxel SM, Sousa KD, Markus RP

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.

Dietary Melatonin Therapy Alleviates the Lamina Cribrosa Damages in Patients With Mild Cognitive Impairments: A Double-Blinded, Randomized Controlled Study.

2020-05 Xu L, Yu H, Sun H, Hu B, Geng Y

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.

2020-05 Ostadmohammadi V, Soleimani A, Bahmani F, Aghadavod E, Ramezani R, Reiter RJ, Mansournia MA, Banikazemi Z, Soleimani M, Zaroudi M, Asemi Z

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.

Clinical Impact of Melatonin on Breast Cancer Patients Undergoing Chemotherapy; Effects on Cognition, Sleep and Depressive Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial.

2020-04 Palmer ACS, Zortea M, Souza A, Santos V, Biazús JV, Torres ILS, Fregni F, Caumo W

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.

The effect of melatonin on depressive symptoms and anxiety in patients after acute coronary syndrome: The MEDACIS randomized clinical trial.

2019-12 Madsen MT, Zahid JA, Hansen CH, Grummedal O, Hansen JR, Isbrand A, Andersen UO, Andersen LJ, Taskiran M, Simonsen E, Gögenur I

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.

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.

2019-11 Palmer ACS, Souza A, Dos Santos VS, Cavalheiro JAC, Schuh F, Zucatto AE, Biazus JV, Torres ILDS, Fregni F, Caumo W

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).

Healthier rhythm, healthier brain? Integrity of circadian melatonin and temperature rhythms relates to the clinical state of brain-injured patients.

2019-08 Blume C, Angerer M, Raml M, Del Giudice R, Santhi N, Pichler G, Kunz AB, Scarpatetti M, Trinka E, Schabus M

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).

Melatonin MT1 receptor as a novel target in neuropsychopharmacology: MT1 ligands, pathophysiological and therapeutic implications, and perspectives.

2019-06 Comai S, Lopez-Canul M, De Gregorio D, Posner A, Ettaoussi M, Guarnieri FC, Gobbi G

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.

Melatonin is a biomarker of circadian dysregulation and is correlated with major depression and fibromyalgia symptom severity.

2019-01 Caumo W, Hidalgo MP, Souza A, Torres ILS, Antunes LC

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).

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