MODERN IDEAS OF “SLOW SLEEP” AND “REM-SLEEP” AND THEIR ROLE IN PATHOGENESIS OF ALZHEIMER’S DISEASE (REVIEW OF LITERATURE)

This review discusses the data of new researches on the functional purpose of sleep and its stages, and its role in the development of pathological conditions. The main modern hypotheses and concepts about a role of slow sleep and REM-sleep (rapid eye movement) are interpreted. The visceral theory of slow sleep as an activator of restorative processes in the brain and manager of internal organs functions is described. A brain "drainage" function of slow sleep is known. Recent studies suggest sleep-wake disturbances, for example, obstructive apnea syndrome, may influence Alzheimer's disease (AD) onset and progression. Possible mechanisms such asfunctional disorders of brain lymphatic system during slow sleep and the extracellular accumulation of the amyloid-ß (Aß) peptide underlying the relationship between the sleep-wake disturbances and AD are described. The role of REM-sleep in the formation of the central nervous system in the early postnatal period and the performance of the function of mental adaptation are discussed. In this article, we presented data about the role both of neurotransmitters and neuropeptides in the regulation of sleep-wake cycle and the maintenance of wakefulness and REM-sleep. The possible new approach to the forecasting of cognitive and emotional-affective disorders in sleep disturbances is substantiated from the perspective of modern neuroscience and sleep neurophysiology still in childhood is justified

INSOMNIA AND CIRCADIAN RHYTHMS OF MELATONIN IN MENOPAUSAL WOMEN

The aim of the review is to analyze literature data about sleep homeostasis and the role of the one of circadian system key elements – melatonin – in the regulation of the sleep-wake cycle in women in menopause. It was shown that the prevalence and structure of sleep disorders depends on the menopausal phase. It was revealed that the melatonin content in the body, determined in various biological media (blood, saliva, urine), depends on age, sex, race, and chronotype. It was shown that morning melatonin can be used as a biological marker for determining the chronotype. Most studies indicated a decrease in melatonin level with aging. Moreover, women have lower melatonin level than men. In case of insomnia, lower melatonin level was found, although the results of the studies are ambiguous. The shift in the peak of hormone secretion in the early morning hours was described in menopausal women. Also, the dependence of melatonin circadian rhythm on the menopausal phase was revealed, which determines different approaches to insomnia therapy. We revealed the association of melatonin secretion circadian rhythms with Clock 3111T/C gene polymorphism in Caucasian patients with insomnia, which allows considering 3111T allele as risky in the formation of melatonin circadian rhythm disturbances in these patients

Free Radical Oxidation and Sleep Disorders in Andro- and Menopause (Literature Review)

This review presents data on changes in the physiology of sleep during reproductive aging. It is noted that insomnia and obstructive sleep apnea syndrome (OSAS) are the main sleep disorders. The results of foreign and domestic studies in the field of free radical oxidation during sleep deprivation in animal models are presented, indicating the dependence of processes on the duration of sleep deprivation. The largest number of studies of free radical processes in a person with somnological pathology was carried out in the study of OSAS. Blood, urine, saliva, condensate of exhaled air can be biomaterial for determining the parameters of free radical oxidation. It was shown that the intensity of oxidative stress depends on the severity of OSAS, as evidenced by the positive correlation of the level of active products of thiobarbituric acid, the products of oxidation of proteins and carbonyl groups with the apnea/hypopnea index, determining the development of not only oxidative, but also carbonyl stress in patients with a severe degree OSAS. Biomarkers such as thioredoxin, malondialdehyde, superoxide dismutase, and reduced iron have shown a more stable relationship between increased oxidative stress and OSA. Despite the results obtained, the question of the association of oxidative stress and hypoxia in OSA remains debatable, which is associated with the opposite results of some studies. Insomnia, which occurs mainly in females, is accompanied by a high level of end products of lipid peroxidation with a decrease in the activity of antioxidants such as paraoxonase, an enzymatic component of the glutathione system. Along with this, menopausal women present low levels of uric acid, which correlates with high scores of the Pittsburgh sleep quality index questionnaire. Recent studies have identified an association between the activity of the «lipoperoxidation – antioxidants» system and the Clock 3111T/C gene polymorphism in menopausal Caucasian women, indicating the protective role of the minor allele

Functional state of glutathione system in menopausal women of the Buryat ethnic group with insomnia

The aim of the study was to assess the functional state of glutathione system in menopausal women of the Buryat ethnic group with insomnia.   Methods. The study involved 94 women aged 45 to 60 years who were divided into perimenopause (n = 44) and postmenopause (n = 50) groups. In each period, a control group and an insomniac group were identified. The reduced (GSH) and oxidized (GSSG) glutathione levels in erythrocyte lysate, the glutathione-S-transferase π concentration and glutathione reductase activity in blood serum were determined.   Results. An increase of the GSH level (p < 0.05) and GSH/GSSG ratio (p < 0.05) both in perimenopausal and postmenopausal women with insomnia were found as compared to controls. There were no differences in the glutathione-depends enzymes parameters. Comparative analysis of the main groups showed an increase GSH/GSSG ratio (p < 0.05) in the postmenopausal period compared with perimenopause.   Conclusion. The study results demonstrate the glutathione link activation in Buryat menopausal women with insomnia. In this regard, the appointment of glutathione preparations for the correction of free radical homeostasis in these groups of women cannot be recommended

Performance of Metabolic Parameters in Formation of Sleep Disorders in Menopausal Women

Background. It is known that menopausal women suffer from sleep disorders. As additional diagnostic methods, it is possible to use the equations of linear classification functions.Aim: to determine the most informative parameters among the lipid profile, the “lipid peroxidation – antioxidant protection” system parameters and the melatonin secretion chronobiological rhythms in menopausal women with sleep disorders.Materials and methods. 56 perimenopausal women and 70 postmenopausal ones in accordance with the inclusion criteria participated in this study. Diagnoses of insomnia and obstructive sleep apnea syndrome were made according to the results of specialized somnological questionnaires and polysomnographic monitoring. Spectrophotometric methods for studying of lipid metabolism and the “lipid peroxidation – antioxidant protection” system parameters, an enzyme immunoassay method for determining melatonin were also used. A multidimensional discriminant analysis to reveal the most informative parameters among the parameters studied was used.Results. The most informative indicators of the metabolic system for sleep disorders in perimenopausal women with insomnia are melatonin 06.00–07.00 h, melatonin 18.00–19.00 h, melatonin 23.00–00.00 h, ketodienes and conjugated trienes, oxidized glutathione; with insomnia and OSAS – melatonin 06.00–07.00 h, melatonin 12.00–13.00 h, melatonin 23.00–00.00 h, substrates with conjugated double bonds, total cholesterol; in postmenopausal women with insomnia – diene conjugates, α-tocopherol, total antioxidant capacity, active products of thiobarbituric acid, reduced glutathione; with insomnia and OSAS – total antioxidant capacity, α-tocopherol, substrates with conjugated double bonds.Conclusions. The results obtained indicate a great strain in the antioxidant protection system in menopausal women with sleep disorders in response to changes in free radical homeostasis

Sleep disorders and obesity in adolescents: peculiarities of psycho-cognitive status (literature review)

Adolescence is a time of important physical, cognitive, emotional, and social changes. Sleep is a primary aspect of adolescent development. Its disorders critically influence adolescents' ability to think, behave, and feel during daytime hours. Daytime activities, changes in the environment, and individual factors can have significant effects on adolescents' sleeping patterns. It is known, that a significant change of the sleep-wake cycle across adolescent development is a tendency to stay up later at night and to sleep in later in the morning. The peculiarity of this period of life is called a sleep delayed phase phenomenon, which can play the important role in the development of eating disorders and cause risk of obesity. The epidemic of childhood obesity presents a major public health problem. Many authors consider that obesity is a multisystem disease with potentially devastating consequences for physical and emotional health across the lifespan. Obesity may cause obstructive sleep apnea syndrome that can result in excessive daytime sleepiness in adolescents and have a negative effect on learning, school performance, and behavior. Early detection of risk factors, screening for metabolic and sleep disturbances in adolescents are major aims in reducing risk of cognitive and behavioral disorders. We assume that further studies of the psycho-cognitive impairments in adolescents with obesity in the sleep-wake continuum are necessary for the development of new approaches to forecasting, early diagnosis and pathogenically therapies of emotional and cognitive changes at the stage of personality formation as well as potentially reversible sleep and metabolic disorders

Glutathione System in Sleep Disorders (Literature Review)

This review examines the variability of the glutathione system in sleep pathologies. Modern sleep theory assumes a restorative sleep function, including active utilization of oxidants and protection from excessive oxidation. In this review article, we conducted an analysis of domestic and foreign literature and summarized  data relating aspects of the functioning of the glutathione system in somnological disorders. Various authors have established systemic oxidative stress in insomnia due to reduced activity of glutathione peroxidase. Also, oxidative stress in insomnia is observed in certain areas of the brain due to a decrease in glutathione levels in them. Studies of the functioning of the glutathione system genes in insomnia, whose polymorphisms may include alleles that inhibit oxidation, are arousing interest. An alternative pattern of changes is observed in obstructive sleep apnea syndrome. The apnea stage affects the indicators of the glutathione system. The values of the glutathione system indicators increase with mild to moderate apnea. This is an adaptive response mechanism. Also, the development of oxidative stress in apnea, which leads to disorders in the glutathione system, is cyclical. As a result, people with apnea do not have sufficient replenishment of the components of the glutathione system during sleep. The existing modification does not allow to fully respond to the intensification of peroxide processes and to restrain the activation of excessive oxidation

Obesity and Circadian Cycle of Sleep and Wakefulness: Common Points and Prospects of Therapy

The prevalence of obesity in recent years has assumed the character of a non-communicable epidemic. Wherein, the standard approaches for its treatment are not always successful. Meanwhile, obesity remains one of the main causes of the formation of a number of some serious diseases, such as cardiovascular, diabetes, cancer, etc. and death from them. In search of alternative and more adequate methods of obesity treatment and preventing its complications, recent studies are aimed at further identifying new associations and revealing the pathophysiological mechanisms underlying excessive weight gain. It should be noted an increasing amount of chronobiological studies that raised awareness of the key role of the body’s circadian rhythms and its main regulator, melatonin, responsible for the temporary organization of the main physiological (including metabolism) processes throughout the 24-h day, in the development and progression of obesity. This review is devoted to the consideration of mutually directed interactions between the circadian system and metabolism; attempts have been made to explain the role of sleep-wake cycle disruptions in the excess accumulation of adipose tissue and the formation of obesity and its comorbidities, as well as detailed therapeutic principles based on normalizing disruption of body clocks using time-coordinated approaches to food intake, physical activity, the effects of non-drug methods and pharmacological substances (chronobiotics), which represents a novel and promising ways to prevent or treat obesity and associated diseases

Obstructive Sleep Apnea Syndrome and Features of the Neurophysiological Sleep Pattern

The high prevalence of obstructive sleep apnea syndrome (OSA) causes a steady interest in this pathology. In recent years, one of the urgent problems in modern somnology is the assessment of the main mechanisms of neuronal dysfunction during the day and at night in OSA, the ideas about which, to a large extent, remain contradictory and not fully understood. One of the modern methods for assessing neuronal dysfunction during sleep is the study of the sleep microstructure, and for its assessment, the method of analysis of cyclic alternating pattern (CAP), an EEG marker of unstable sleep, is used. The cyclic alternating pattern is found both in the sleep of adults and children with various sleep disorders and, in particular, with OSAS, therefore, it is a sensitive tool for studying sleep disorders throughout life. With the elimination of night hypoxia against the background of CPAP therapy, the sleep microstructure is restored, the spectral characteristics of the EEG change, and a decrease in the number of EEG arousals after treatment leads to the restoration of daytime functioning. Understanding the role of short-term EEG activations of the brain during sleep can provide significant data on sleep functions in health and disease. Despite the improving diagnosis of sleep disorders using machine algorithms, assessing the relationship of structures and functions of the brain during sleep, neurophysiological data are not entirely clear, which requires further research. In this review, we tried to analyze the results of the main studies of the neurophysiological sleep pattern in OSA against the background of respiratory support during sleep

Levels of Advanced Oxidation Protein Products in Blood Plasma of Peri- and Postmenopausal Women with Insomnia

Background. Insomnia occurs in more than half of menopausal women. These disorders can contribute to a change in the prooxidant-antioxidant balance, causing the damage to structural cellular elements. Currently, there is a lack of research on this issue.Aim. To carry out a comparative analysis of the level of advanced oxidation protein products in in periand postmenopausal women with insomnia.Materials and methods. The study included peri(n = 30) and postmenopausal (n = 60) women, who were divided into 2 groups (control and main groups) in each menopausal phase after being questioned using special sleep questionnaires: Insomnia Severity Index; Epworth Sleepiness Scale; Munich Chronotype Questionnaire. The advanced oxidation protein products (AOPP) levels was determined by immunoenzymatic assay using ImmunDiagnostik (German) kits on a BioTek EL×808 (USA) analyzer. Statistical analysis was performed using Mann – Whitney test.Results. Comparative analysis of the AOPP levels in control groups, depending on the menopausal periods, showed an increase in their levels in the postmenopausal period as compared to perimenopause (p < 0.05). When comparing the AOPP levels between the control and the main group in different menopausal periods, statistically significant differences were revealed only in the perimenopausal period towards a higher content in women with insomnia (p < 0.05). The presence of insomnia in postmenopausal women is accompanied by a higher AOPP levels as compared to the perimenopausal women (p < 0.05).Conclusion. The obtained results indicate the association between insomnia and oxidative proteins modification only in the perimenopausal period