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

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. There is a wide range of sleep disturbances in patients with PD, such as insomnia and rapid eye movement (REM) sleep behavior disorder (or REM behavior disorder (RBD)). RBD is a sleep disorder in which a patient acts out his/her dreams and includes abnormal behaviors during the REM phase of sleep. On the other hand, melatonin is the principal hormone that is secreted by the pineal gland and significantly modulates the circadian clock and mood state. Furthermore, melatonin has a wide range of regulatory effects and is a safe treatment for sleep disturbances such as RBD in PD. However, the molecular mechanisms of melatonin involved in the treatment or control of RBD are unknown. In this study, we reviewed the pathophysiology of PD and sleep disturbances, including RBD. We also discussed the potential molecular mechanisms of melatonin involved in its therapeutic effect. It was concluded that disruption of crucial neurotransmitter systems that mediate sleep, including norepinephrine, serotonin, dopamine, and GABA, and important neurotransmitter systems that mediate the REM phase, including acetylcholine, serotonin, and norepinephrine, are significantly involved in the induction of sleep disturbances, including RBD in PD. It was also concluded that accumulation of α-synuclein in sleep-related brain regions can disrupt sleep processes and the circadian rhythm. We suggested that new treatment strategies for sleep disturbances in PD may focus on the modulation of α-synuclein aggregation or expression.

Mood and behavior regulation: interaction of lithium and dopaminergic system.

Lithium is one of the most effect mood-stabilizing drugs prescribed especially for bipolar disorder. Lithium has wide range effects on different molecular factors and neural transmission including dopaminergic signaling. On the other hand, mesolimbic and mesocortical dopaminergic signaling is significantly involved in the pathophysiology of neuropsychiatric disorders. This review article aims to study lithium therapeutic mechanisms, dopaminergic signaling, and the interaction of lithium and dopamine. We concluded that acute and chronic lithium treatments often reduce dopamine synthesis and level in the brain. However, some studies have reported conflicting results following lithium treatment, especially chronic treatment. The dosage, duration, and type of lithium administration, and the brain region selected for measuring dopamine level were not significant differences in different chronic treatments used in previous studies. It was suggested that lithium has various mechanisms affecting dopaminergic signaling and mood, and that many molecular factors can be involved, including brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), ß-catenin, protein kinase B (Akt), and glycogen synthase kinase-3 beta (GSK-3ß). Thus, molecular effects of lithium can be the most important mechanisms of lithium that also alter neural transmissions including dopaminergic signaling in mesolimbic and mesocortical pathways.

Opioid receptor µ, not δ and κ, modulate food intake induced by ghrelin in laying chickens.

Evidence from animal studies suggests that the opioidergic system and ghrelin have a regulatory role in food intake, but their interaction(s) have not been studied in laying chickens. So in this study, four experiments (each included four groups) were designed. The first experiment was performed to evaluate the effect of ghrelin on the cumulative food intake. Experiments 2-4 were designed to investigate the possibility of µ, δ, or κ opioid receptors mediating ghrelin-induced hypophagia. All drugs were injected intracerebroventricularly (ICV) at 5 days of age. The results of this study showed that the ICV injection of 1.5 nmol ghrelin did not affect cumulative food intake. However, ICV injection of ghrelin with doses of 3 and 6 nmol significantly reduced the cumulative food intake (p < 0.05). However, co-injection of ghrelin with naltrindole and norbinaltorphimine did not show a significant change in decreased food intake compared with ghrelin. Also, opioid µ receptor gene expression significantly increased (p < 0.05), but δ and κ opioid receptors' gene expression did not significantly change. These results indicated that the opioidergic system is involved in developing ghrelin-induced hypophagic effects in laying chickens. Accordingly, this effect of ghrelin to modify the nutritional behavior is possibly mediated by opioid µ receptor.