Neuroprotective Effect of Melatonin on Sleep Disorders Associated with Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a complex, multisystem disorder with both neurologic and systemic manifestations, which is usually associated with non-motor symptoms, including sleep disorders. Such associated sleep disorders are commonly observed as REM sleep behavior disorder, insomnia, sleep-related breathing disorders, excessive daytime sleepiness, restless legs syndrome and periodic limb movements. Melatonin has a wide range of regulatory effects, such as synchronizing circadian rhythm, and is expected to be a potential new circadian treatment of sleep disorders in PD patients. In fact, ongoing clinical trials with melatonin in PD highlight melatonin’s therapeutic effects in this disease. Mechanistically, melatonin plays its antioxidant, anti-inflammatory, anti-excitotoxity, anti-synaptic dysfunction and anti-apoptotic activities. In addition, melatonin attenuates the effects of genetic variation in the clock genes of Baml1 and Per1 to restore the circadian rhythm. Together, melatonin exerts various therapeutic effects in PD but their specific mechanisms require further investigations.

The Devastating Effects of Sleep Deprivation on Memory: Lessons from Rodent Models

“…A modified multi-platform method was used to subject rats to SD for 1, 3, 5, and 7 days; results showed that the memory capacity of the rats decreased as the SD duration increased. The HE staining revealed significant structural damage to hippocampal neurons, as well as an increase in phosphorylated p38MAPK-positive cells, suggesting that SD could activate p38MAPK in the hippocampal area and mediate the process of SD damage to neuronal cells [ 95 ]. Another study found that SD negatively affects memory function, which may be related to lower levels of the AKAP150 protein in the hippocampus and decreased AMPA receptor activity [ 96 ].…”

“…SD significantly increased the ROS, MDA, and MPO levels in the hippocampus of mice and decreased the activities of SOD, GPx, GSH, and GSH-Px enzymes. SD could be responsible for abnormal metabolism of hippocampal tissue, enhanced lipid oxidation, and lesioned hippocampal tissue [ 95 , 119 ]. Moreover, SD significantly increased the levels of TBARS and GSSG and decreased the GSH/GSSG ratio and the catalase activity, suggesting that SD could reduce antioxidant mechanisms and impair short- and long-term memory [ 114 ].…”

Parkinson’s Disease: A Narrative Review on Potential Molecular Mechanisms of Sleep Disturbances, REM Behavior Disorder, and Melatonin

“…[202] Down-regulation of melatonin receptors in the brain regions affected by PD has been shown. [217] Melatonin level is related to hypothalamic gray matter volume loss and disease severity. [211] Hypothalamic volume loss (also seen in PD) may be responsible for reduced melatonin output.…”

Changes in the Secretion of Melatonin and Selected Adipokines during the Progression of Parkinson’s Disease—Preliminary Studies

“…Some novel research has discovered that melatonin can greatly improve subjective and objective quality of sleep, and has therefore shown promise in reducing the severity of insomnia among patients with PD [ 17 , 18 ]. According to the paper published by Hu et al [ 19 ], there are currently around eight clinical trials registered on clinicaltrials.gov and the EU Clinical Trials Register which are investigating the therapeutic potential of melatonin and its analogues for treating sleep disorders that are commonly associated with PD.…”