scholarly journals Therapeutic aspects of melatonin applications

2021 ◽  
pp. 80-84
Author(s):  
S. L. Tsenteradze ◽  
M. G. Poluektov
Keyword(s):  
Circadian Rhythms ◽  
Pineal Gland ◽  
Biological Clock ◽  
Rapid Change ◽  
Cerebrovascular Diseases ◽  
The Body ◽  
Sleep Wake Disorders ◽  
Hormonal Function ◽  
Cyclic Processes ◽  
Multicenter Clinical Trials

The results of multicenter clinical trials show the broad potential of melatonin since discovery of this adaptogen to the present day. Melatonin is a neuropeptide that is synthesized mainly in the small brain gland, the pineal gland, and has a unique effect in humans and animals. Using melatonin, the pineal gland participates in the organization of circadian periodism and regulation of cyclic processes, acting as an intermediary between the pacemaker mechanism of the suprachiasmatic nuclei (SCN) and peripheral organs. The pineal gland and the SCN of the hypothalamus form part of the system of the so-called biological clock of the body, which plays a key role in the mechanisms of regulation of the biological clock via circadian rhythms and ageing. Initially, melatonin was only considered a hormone involved in the synchronization of the mechanisms of the circadian rhythm, but later it was found that, in addition to this hormonal function, it takes part in the regulation of the seasonal cycle in animals and humans.At present, melatonin drugs have shown high efficacy and safety in various sleep-wake disorders regardless of their genesis, disorganization of circadian rhythms, stress adjustment disorders, rapid change of time zones, shift work and in complex therapy of patients with cerebrovascular diseases.The article considers the multimodal capabilities of melatonin, including adaptogenic, biorhythmogenic, hypnotic, immunostimu-lating, antioxidant effects. The role of melatonin in the treatment of various central nervous system disorders, including neurodegenerative diseases, has been determined.The review emphasizes the wide-ranging effects of melatonin and offers great opportunities for measuring melatonin as a biomarker for early detection and follow-up of various diseases.

scholarly journals Sleep as a biological rhythm: clinical aspects

2021 ◽  
pp. 56-61
Author(s):  
A. N. Puchkova ◽  
M. G. Poluektov
Keyword(s):  
Circadian Rhythms ◽  
Negative Impact ◽  
Biological Clock ◽  
Well Being ◽  
The Body ◽  
Clinical Aspects ◽  
Poor Sleep ◽  
Physical And Mental Health ◽  
Clinical Criteria ◽  
Falling Asleep

Insomnia is a widespread disorder affecting not only sleep quantity and quality, but also daytime well-being and performance, as well as having a negative impact on physical and mental health. Many people have problems falling asleep and maintaining sleep that do not reach the clinical criteria of insomnia. For all the prevalence of such sleep disorders, specialists often overlook a fundamentally important factor that affects sleep and wakefulness cycle, ease of falling asleep and daytime performance. These are circadian rhythms of the body under the control of the biological clock.This review highlights the specifics of the human biological clock and its relationship to insomnia and complaints of poor sleep. The phenomenon of the human chronotype as a set of individual preferences in sleep-wake rhythm is considered. Late chronotype, tat tends to wake up late and be active in the evening turns out to be the most vulnerable to the appearance of complaints of poor sleep and development of insomnia. This result is typical for different age groups. The reason for problems sleep for the late chronotype is the need to adjust to social demands and to fall asleep and wake up too early relative to the phase of one’s own circadian rhythm.Circadian rhythms may contribute to the formation and maintenance of insomnia. Both chronic and acute insomnia may have a chronobiological component that is not always considered. Late chronotype may be a factor further exacerbating the course of insomnia. The regularity of circadian rhythms may also be impaired in insomnia.The importance of the biological clock in the regulation of sleep and wakefulness also explains the successful approach to insomnia treatment with melatonin, which plays an important signaling role in the circadian regulation of the body.

The Biological Clock and Sleep in the Elderly

2006 ◽  
Vol 19 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Myriam Juda ◽  
Mirjam Münch ◽  
Anna Wirz-Justice ◽  
Martha Merrow ◽  
Till Roenneberg
Keyword(s):  
Circadian Rhythms ◽  
Biological Clock ◽  
The Elderly ◽  
Early Morning ◽  
Behavioral Changes ◽  
Older Age ◽  
Age Related ◽  
Theoretical Considerations ◽  
Sleep Difficulties ◽  
Circadian Biology

Abstract: Among many other changes, older age is characterized by advanced sleep-wake cycles, changes in the amplitude of various circadian rhythms, as well as reduced entrainment to zeitgebers. These features reveal themselves through early morning awakenings, sleep difficulties at night, and a re-emergence of daytime napping. This review summarizes the observations concerning the biological clock and sleep in the elderly and discusses the documented and theoretical considerations behind these age-related behavioral changes, especially with respect to circadian biology.

Melatonin Modulates Lactation by Regulating Prolactin Secretion Via Tuberoinfundibular Dopaminergic Neurons in the Hypothalamus- Pituitary System

2020 ◽  
Vol 21 (8) ◽  
pp. 744-750 ◽  
Author(s):  
Hongyang Li ◽  
JingyaWei ◽  
Fengtao Ma ◽  
Qiang Shan ◽  
Duo Gao ◽  
...  
Keyword(s):  
Pineal Gland ◽  
Pituitary Gland ◽  
Antioxidant Capacity ◽  
Dopaminergic Neurons ◽  
Growth And Development ◽  
Endocrine System ◽  
Mammary Glands ◽  
Prolactin Secretion ◽  
The Body ◽  
Stimulation Of

In-depth studies have identified many hormones important for controlling mammary growth and maintaining lactation. One of these is melatonin, which is synthesized and secreted by the pineal gland to regulate circadian rhythms, improve antioxidant capacity, and enhance immunity. Prolactin is secreted by the pituitary gland and is associated with the growth and development of mammary glands as well as initiation and maintenance of lactation. The hypothalamus-pituitary system, the most important endocrine system in the body, regulates prolactin secretion mainly through dopamine released from tuberoinfundibular dopaminergic neurons. This review provides a reference for further study and describes the regulation of lactation and prolactin secretion by melatonin, primarily via the protection and stimulation of tuberoinfundibular dopaminergic neurons.

Nonphotic entrainment of the human circadian pacemaker

1998 ◽  
Vol 274 (4) ◽  
pp. R991-R996 ◽  
Author(s):  
Elizabeth B. Klerman ◽  
David W. Rimmer ◽  
Derk-Jan Dijk ◽  
Richard E. Kronauer ◽  
Joseph F. Rizzo ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Light Exposure ◽  
Core Body Temperature ◽  
Biological Clock ◽  
Bright Light ◽  
Circadian Pacemaker ◽  
Temperature Rhythms ◽  
Blind Individuals ◽  
Nonphotic Entrainment ◽  
Core Body

In organisms as diverse as single-celled algae and humans, light is the primary stimulus mediating entrainment of the circadian biological clock. Reports that some totally blind individuals appear entrained to the 24-h day have suggested that nonphotic stimuli may also be effective circadian synchronizers in humans, although the nonphotic stimuli are probably comparatively weak synchronizers, because the circadian rhythms of many totally blind individuals “free run” even when they maintain a 24-h activity-rest schedule. To investigate entrainment by nonphotic synchronizers, we studied the endogenous circadian melatonin and core body temperature rhythms of 15 totally blind subjects who lacked conscious light perception and exhibited no suppression of plasma melatonin in response to ocular bright-light exposure. Nine of these fifteen blind individuals were able to maintain synchronization to the 24-h day, albeit often at an atypical phase angle of entrainment. Nonphotic stimuli also synchronized the endogenous circadian rhythms of a totally blind individual to a non-24-h schedule while living in constant near darkness. We conclude that nonphotic stimuli can entrain the human circadian pacemaker in some individuals lacking ocular circadian photoreception.

Clock gene-independent daily regulation of haemoglobin oxidation in red blood cells

2021 ◽  
Author(s):  
Andrew D. Beale ◽  
Priya Crosby ◽  
Utham K. Valekunja ◽  
Rachel S. Edgar ◽  
Johanna E. Chesham ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Human Subjects ◽  
Developmental Regulation ◽  
Physiological Role ◽  
Cell Types ◽  
The Body

AbstractCellular circadian rhythms confer daily temporal organisation upon behaviour and physiology that is fundamental to human health and disease. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body. Being naturally anucleate, RBC circadian rhythms share key elements of post-translational, but not transcriptional, regulation with other cell types. The physiological function and developmental regulation of RBC circadian rhythms is poorly understood, however, partly due to the small number of appropriate techniques available. Here, we extend the RBC circadian toolkit with a novel biochemical assay for haemoglobin oxidation status, termed “Bloody Blotting”. Our approach relies on a redox-sensitive covalent haem-haemoglobin linkage that forms during cell lysis. Formation of this linkage exhibits daily rhythms in vitro, which are unaffected by mutations that affect the timing of circadian rhythms in nucleated cells. In vivo, haemoglobin oxidation rhythms demonstrate daily variation in the oxygen-carrying and nitrite reductase capacity of the blood, and are seen in human subjects under controlled laboratory conditions as well as in freely-behaving humans. These results extend our molecular understanding of RBC circadian rhythms and suggest they serve an important physiological role in gas transport.

PEPTIDE REGULATES HUMAN CIRCADIAN RHYTHMS GENES EXPRESSION DURING PINEAL GLAND ACCELERATED AGING

2020 ◽  
pp. 429-435
Author(s):  
О. М. Ивко ◽  
Н. С. Линькова ◽  
А. Р. Ильина ◽  
А. А. Шарова ◽  
Г. А. Рыжак
Keyword(s):  
Circadian Rhythms ◽  
Pineal Gland ◽  
Circadian Clock ◽  
Peripheral Blood ◽  
Accelerated Aging ◽  
Peripheral Blood Lymphocytes ◽  
Circadian Genes ◽  
Blood Lymphocytes ◽  
Aged People ◽  
Genes Expression

Ночная работа приводит к десинхронизации биоритмов, нарушению мелатонинобразующей функции и ускоренному старению эпифиза человека. Одним из перспективных геропротекторов, восстанавливающих синтез эпифизарного мелатонина, является пептид AEDG ( Ala-Glu-Asp-Gly ). Последний в 1,7 раза повышает экскрецию 6-сульфатоксимелатонина в моче людей среднего возраста, у которых этот показатель исходно снижен. Кроме того, у людей со сниженной мелатонинобразующей функцией эпифиза, пептид AEDG нормализует повышенную экспрессию циркадных генов Clock и Csnk 1 e в лейкоцитах и в 2 раза повышает сниженную экспрессию гена Cry 2 в лимфоцитах крови. В основе геропротекторного эффекта пептида AEDG лежит его способность восстанавливать мелатонинобразующую функцию эпифиза через регуляцию экспрессии часовых генов человека. Night work provides biorhythms desynchronization, disorder of melatonin-producing function and accelerated pineal gland aging. One of the promising geroprotectors restoring the pineal melatonin synthesis is the AEDG ( Ala-Glu-Asp-Gly ) peptide. AEDG peptide increases in 1,7 times the 6-sulfatoxymelatonin (6-SOMT) excretion in the urine of middle-aged people. Moreover, AEDG peptide normalized circadian Clock and Csnk1e genes hyper expression in leukocytes in 1,9-2,1 times and increases the Cry 2 gene hypo expression in peripheral blood lymphocytes in 2 times in people with reduced melatonin-producing epiphysis function. The geroprotective effect of the AEDG peptide is based on its ability to restore the epiphysis melatonin-producing function by means regulation of human circadian genes expression.

scholarly journals Spontaneous HTLV-1 transcription is accompanied by distinct epigenetic changes in the 5′ and 3′ long terminal repeats

2018 ◽  
Vol 3 ◽  
pp. 105 ◽  
Author(s):  
Michi Miura ◽  
Paola Miyazato ◽  
Yorifumi Satou ◽  
Yuetsu Tanaka ◽  
Charles R.M. Bangham
Keyword(s):  
Histone Modifications ◽  
Insertion Site ◽  
Rapid Change ◽  
Epigenetic Modifications ◽  
The Body ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Long Terminal Repeats ◽  
Terminal Repeats ◽  
The Impact

Background:The human retrovirus HTLV-1 inserts the viral complementary DNA of 9 kb into the host genome. Both plus- and minus-strands of the provirus are transcribed, respectively from the 5′ and 3′ long terminal repeats (LTR). Plus-strand expression is rapid and intense once activated, whereas the minus-strand is transcribed at a lower, more constant level. To identify how HTLV-1 transcription is regulated, we investigated the epigenetic modifications associated with the onset of spontaneous plus-strand expression and the potential impact of the host factor CTCF.Methods:Patient-derived peripheral blood mononuclear cells (PBMCs) and in vitro HTLV-1-infected T cell clones were examined. Cells were stained for the plus-strand-encoded viral protein Tax, and sorted into Tax+and Tax–populations. Chromatin immunoprecipitation and methylated DNA immunoprecipitation were performed to identify epigenetic modifications in the provirus. Bisulfite-treated DNA fragments from the HTLV-1 LTRs were sequenced. Single-molecule RNA-FISH was performed, targeting HTLV-1 transcripts, for the estimation of transcription kinetics. The CRISPR/Cas9 technique was applied to alter the CTCF-binding site in the provirus, to test the impact of CTCF on the epigenetic modifications.Results:Changes in the histone modifications H3K4me3, H3K9Ac and H3K27Ac were strongly correlated with plus-strand expression. DNA in the body of the provirus was largely methylated except for the pX and 3′ LTR regions, regardless of Tax expression. The plus-strand promoter was hypomethylated when Tax was expressed. Removal of CTCF had no discernible impact on the viral transcription or epigenetic modifications.Conclusions:The histone modifications H3K4me3, H3K9Ac and H3K27Ac are highly dynamic in the HTLV-1 provirus: they show rapid change with the onset of Tax expression, and are reversible. The HTLV-1 provirus has an intrinsic pattern of epigenetic modifications that is independent of both the provirus insertion site and the chromatin architectural protein CTCF which binds to the HTLV-1 provirus.

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