Melatonin, the neurohormone of the pineal gland, is also produced by various other tissues and cells. It acts via G protein-coupled receptors expressed in various areas of the central nervous system and in peripheral tissues. Parallel signaling mechanisms lead to cell-specific control and recruitment of downstream factors, including various kinases, transcription factors and ion channels. Additional actions via nuclear receptors and other binding sites are likely. By virtue of high receptor density in the circadian pacemaker, melatonin is involved in the phasing of circadian rhythms and sleep promotion. Additionally, it exerts effects on peripheral oscillators, including phase coupling of parallel cellular clocks based on alternate use of core oscillator proteins. Direct central and peripheral actions concern the up- or downregulation of various proteins, among which inducible and neuronal NO synthases seem to be of particular importance for antagonizing inflammation and excitotoxicity. The methoxyindole is also synthesized in several peripheral tissues, so that the total content of tissue melatonin exceeds by far the amounts in the circulation. Emerging fields in melatonin research concern receptor polymorphism in relation to various diseases, the control of sleep, the metabolic syndrome, weight control, diabetes type 2 and insulin resistance, and mitochondrial effects. Control of electron flux, prevention of bottlenecks in the respiratory chain and electron leakage contribute to the avoidance of damage by free radicals and seem to be important in neuroprotection, inflammatory diseases and, presumably, aging. Newly discovered influences on sirtuins and downstream factors indicate that melatonin has a role in mitochondrial biogenesis.

No abstract

Good sleep is necessary for good physical and mental health and a good quality of life. Insufficient sleep is a pervasive and prominent problem in the modern 24-h society. A considerable body of evidence suggests that insufficient sleep causes hosts of adverse medical and mental dysfunctions. An extensive literature search was done in all the major databases for “insufficient sleep” and “public health implications” in this review. Globally, insufficient sleep is prevalent across various age groups, considered to be a public health epidemic that is often unrecognized, under-reported, and that has rather high economic costs. This paper addresses a brief overview on insufficient sleep, causes, and consequences, and how it adds to the existing burden of diseases. Insufficient sleep leads to the derailment of body systems, leading to increased incidences of cardiovascular morbidity, increased chances of diabetes mellitus, obesity, derailment of cognitive functions, vehicular accidents, and increased accidents at workplaces. The increased usage of smart phones and electronic devices is worsening the epidemic. Adolescents with insufficient sleep are likely to be overweight and may suffer from depressive symptoms. The paper concludes by emphasizing sleep quality assessments as an important early risk indicator, thereby reducing the incidence of a wide spectrum of morbidities.

The pineal product melatonin has remarkable antioxidant properties. It is secreted during darkness and plays a key role in various physiological responses including regulation of circadian rhythms, sleep homeostasis, retinal neuromodulation and vasomotor responses. It scavenges hydroxyl, carbonate and various organic radicals as well as a number of reactive nitrogen species. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes including superoxide dismutase, glutathione peroxidase and glutathione reductase, and by augmenting glutathione levels. Melatonin preserves mitochondrial homeostasis, reduces free radical generation and protects mitochondrial ATP synthesis by stimulating Complex I and IV activities. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases. The efficacy of melatonin in preventing oxidative damage in either cultured neuronal cells or in the brains of animals treated with various neurotoxic agents, suggests that melatonin has a potential therapeutic value as a neuroprotective drug in treatment of Alzheimer´s disease (AD), Parkinson´s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington´s disease (HD), stroke and brain trauma. Therapeutic trials with melatonin indicate that it has a potential therapeutic value as a neuroprotective drug in treatment of AD, ALS and HD. In the case of other neurological conditions, like PD, the evidence is less compelling. Melatonin's efficacy in combating free radical damage in the brain suggests that it can be a valuable therapeutic agent in the treatment of cerebral edema following traumatic brain injury or stroke. Clinical trials employing melatonin doses in the range of 50-100 mg/day are warranted before its relative merits as a neuroprotective agent is definitively established.

No abstract