Circadian disruption
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The lifestyle of human society is drifting apart from the natural environmental cycles that have influenced it since its inception. These cycles were fundamental in structuring the daily lives of people in the pre-industrial era, whether they were seasonal or daily. Factors that disrupt the regularity of human behaviour and its alignment with solar cycles, such as late night activities accompanied with food intake, greatly disturb the internal temporal organization in the body. This is believed to contribute to the rise of the so-called diseases of civilization. In this review, we discuss the connection between misalignment in daily (circadian) regulation and its impact on health, with a focus on cardiovascular and metabolic disorders. Our aim is to review selected relevant research findings from laboratory and human studies to assess the extent of evidence for causality between circadian clock disruption and pathology. Keywords: Circadian clock, Chronodisruption, Metabolism, Cardiovascular disorders, Spontaneously hypertensive rat, Human, Social jetlag, Chronotype.
- MeSH
- chronobiologické poruchy patofyziologie metabolismus komplikace MeSH
- cirkadiánní hodiny fyziologie MeSH
- cirkadiánní rytmus * fyziologie MeSH
- kardiovaskulární nemoci * metabolismus etiologie epidemiologie patofyziologie MeSH
- lidé MeSH
- metabolické nemoci * metabolismus epidemiologie patofyziologie etiologie MeSH
- modely nemocí na zvířatech MeSH
- rizikové faktory MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Biologické cirkadiánní hodiny mají všichni obratlovci, včetně člověka. Jejich receptory jsou na oční sítnici, informace o střídání dne a noci jsou vedeny do centra v hypothalamu a odtud do epifýzy. Ta produkuje hormon melatonin (N-acetyl-5-metoxytryptamin), téměř výhradně v období tmavé části dne. Hormon je rychle vyplavován do krve a mozkomíšního moku a je bezprostředním nosičem informace o fázi cirkadiánního cyklu buňkám celého těla, které podřizují fyziologické funkce orgánů a organismu střídání dne a noci. Podle dosavadních výzkumů se melatonin účastní řady významných fyziologických funkcí: regulace spánku a cirkadiánních rytmů, nálady, imunitní, onkostatické a antioxidační aktivity. Syntéza melatoninu klesá s věkem. Umělé osvětlení večer nebo brzy ráno zkracuje tmavou část dne, také jen krátkodobé rozsvícení v noci redukuje množství melatoninu produkovaného během 24 hodin. Syntézu melatoninu významně narušuje letecký přesun přes několik časových zón. Zdravotní následky narušení biologických rytmů zahrnují poruchy spánku, zvýšený výskyt některých zhoubných nádorů, obezity, metabolického syndromu, diabetu, zhoršení projevů některých neurodegenerativních onemocnění. V primární prevenci je třeba omezovat noční směny a edukovat veřejnost o významu nočního spánku.
All vertebrates, including humans, have a biological circadian clock. Their receptors are located on the retina, and information regarding the alternation of day and night are transferred to a centre in the hypothalamus and from there into the pineal gland which produces melatonin (N-acetyl-5-metoxytryptamin), almost exclusively during the hours of darkness. The hormone is quickly discharged into the bloodstream and cerebrospinal fluid into all cells. Such immediate information about the circadian phase of day/night changes allows to organs and organism to regulate their physiological functions. Current research suggests that melatonin is involved in several important physiological functions: sleep regulation and circadian rhythms, mood, immunity, oncostatic and antioxidant activities. Synthesis of melatonin reduces with age. Artificial light in the evenings and early mornings reduces the dark part of the day and even brief use of artificial light at night reduces the levels of melatonin produced over a 24-hour period. Air transport over a number of time-zones likewise significantly disrupts melatonin production. The health consequences of the disruption of biologcal rhythms include sleep disorders, higher frequency of some types of cancer, obesity, metabolic syndrome, diabetes and aggravation of some neurodegenerative symptoms. In primary prevention it is necessary to limit the duration of night shifts and educate the public on the importance of night sleep.
- MeSH
- chronobiologické poruchy * etiologie komplikace prevence a kontrola MeSH
- cirkadiánní hodiny * fyziologie MeSH
- cirkadiánní rytmus fyziologie MeSH
- lidé MeSH
- melatonin * nedostatek sekrece terapeutické užití MeSH
- nádory etiologie prevence a kontrola MeSH
- poruchy spánku a bdění etiologie prevence a kontrola MeSH
- primární prevence * metody MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The circadian system comprises the central clock, located in the suprachiasmatic nucleus of the hypothalamus, and the peripheral clocks in various tissues that are interconnected; together they coordinate many daily activities, including sleep and wakefulness, physical activity, food intake, glucose sensitivity and cardiovascular functions. Disruption of circadian regulation seems to be associated with metabolic disorders (particularly impaired glucose tolerance) and cardiovascular disease. Previous clinical trials revealed that disturbance of the circadian system, specifically due to shift work, is associated with an increased risk of type 2 diabetes mellitus. This review is intended to provide clinicians who wish to implement knowledge of circadian disruption in diagnosis and strategies to avoid cardio-metabolic disease with a general overview of this topic.
- MeSH
- chronobiologické poruchy patofyziologie komplikace MeSH
- cirkadiánní rytmus * fyziologie MeSH
- diabetes mellitus 2. typu patofyziologie metabolismus MeSH
- kardiovaskulární nemoci * etiologie patofyziologie MeSH
- lidé MeSH
- metabolické nemoci * patofyziologie metabolismus etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Teorie sociálních zeitgeberů se mimo jiné zabývá hledáním souvislostí, jak se mohou stresové životní události podílet na rozvoji depresivních epizod. Podle této teorie vedou k narušení sociálních rytmů a zpětně i biologických rytmů. V rámci této teorie je též zvažován vztah k hypomanickým a manickým epizodám a otázkou zůstává, zda je přítomné narušení cirkadiánních rytmů způsobeno pouze vnitřními mechanismy, ke kterým řadíme poruchy funkce nucleus suprachiasmaticus. Klinickým využitím teorie sociálních zeitgeberů v praxi je interpersonální terapie a terapie sociálních rytmů (IPSRT). Kromě toho se objevují i nové farmakologické možnosti, založené na obnově narušeného cirkadiánního rytmu. Příkladem je moderní antidepresivum agomelatin, jehož aplikace může zásadně přispět ke zvýšení kvality antidepresivní léčby včetně výrazného pozitivního efektu při dosahování remise onemocnění a jejího dlouhodobého udržení.
The social zeitgeber theory offers an explanation of how life events trigger depressive episodes. According to this theory, life stress leads to mood episodes by causing disruptions in individuals' social routines and, in turn, their biological circadian rhythms. In this article is also reviewed the evidence that this theory may be applied to (hypo)manic episodes and whether circadian rhythm disruptions are triggered by an internal mechanism, such as an abnormality in ones pacemaker (the suprachiasmatic nucleus). Interpersonal therapy and therapy of social rhythms (IPRST) are the clinical implications of social zeitgebers theory. Furthermore, the new pharmacologic approaches, such as new antidepressant agomelatin, based on restoration of dysrupted circadian rhythms, can contribute to clinical profit for depressive patients, including the positive effect on remission.
- Klíčová slova
- cirkadiánní systém, agomelatin, chronobiologie, afektivní poruchy, zeitgeber,
- MeSH
- acetamidy terapeutické užití MeSH
- behaviorální terapie metody MeSH
- biologické hodiny fyziologie účinky léků MeSH
- chronobiologické poruchy etiologie komplikace MeSH
- činnosti denního života psychologie MeSH
- cirkadiánní rytmus fyziologie účinky léků MeSH
- depresivní poruchy etiologie farmakoterapie psychologie MeSH
- financování organizované MeSH
- interpersonální vztahy MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- melatonin sekrece MeSH
- poruchy nálady etiologie komplikace MeSH
- psychiatrie trendy MeSH
- psychický stres komplikace MeSH
- psychologická teorie MeSH
- sociální chování MeSH
- životní změny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Huntingtonova choroba (Huntington disease; HD) je autozomálně dominantní, dědičné neurodegenerativní onemocnění s fatální prognózou. Kromě typicky progresivně se zhoršujících motorických funkcí lze u pacientů s HD pozorovat i kognitivní a behaviorální poruchy. Mezi nejčastější symptomy patří také poruchy spánku, které mají velmi závažný dopad na kvalitu života jak pacientů, tak jejich blízkých a které bývají asociovány s narušeným cirkadiánním systémem. Stabilizace délky i kvality spánku posílením cirkadiánního systému by mohla zmírnit či potlačit mnohé symptomy HD, jež mají sice přímou příčinu v etiologii HD, sekundárně mohou být ale zesíleny dlouhodobým nedostatečným spánkem či právě poruchami cirkadiánního systému. U premanifestujících pacientů by takové zásahy mohly vést k pomalejšímu rozvoji či nástupu zejména kognitivních symptomů nemoci. Terapie synchronizujícím jasným světlem, která se již osvědčila jako doplňkový nástroj k léčbě afektivních i některých neurodegenerativních nemocí, by mohla vést k radikálnímu zlepšení života pacientů alespoň v počátečních stadiích onemocnění.
Huntington disease (HD) is an autosomal-dominant, hereditary neurodegenerative disease with a fatal prognosis. Besides the typical progressive deterioration of motor functions, cognitive and behavioral disorders can also be observed in patients with HD. The most common symptoms also include sleep disorders that seriously affect the quality of life of the patients but also of their relatives and which are being associated with a disrupted circadian system. Stabilization of sleep lenght and quality by strengthening the circadian system could mitigate or suppress many HD symptoms, which, although being a direct result of the disease etiology, can secondarily be heightened by long-term insufficient sleep or circadian system disturbances. Such interventions could lead to slower especially cognitive symptom progression or onset in pre-manifesting patients. Synchronizing bright light therapy, which has already proven useful as a complementary tool for the treatment of affective disorders, as well as some neurodegenerative diseases, could lead to radical improvement of the patients‘ quality of life, at least in the early stages of disease development.
- Klíčová slova
- hodinové geny,
- MeSH
- cirkadiánní hodiny MeSH
- fototerapie metody MeSH
- Huntingtonova nemoc * komplikace terapie MeSH
- lidé MeSH
- poruchy spánku a bdění terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
The choroid plexus (ChP) in the brain ventricles has a major influence on brain homeostasis. In this study, we aimed to determine whether the circadian clock located in ChP is affected by chronodisruption caused by misalignment with the external light/dark cycle and/or inflammation. Adult mPer2Luc mice were maintained in the LD12:12 cycle or exposed to one of two models of chronic chronodisruption - constant light for 22-25 weeks (cLL) or 6-hour phase advances of the LD12:12 cycle repeated weekly for 12 weeks (cLD-shifts). Locomotor activity was monitored before the 4th ventricle ChP and suprachiasmatic nuclei (SCN) explants were recorded in real time for PER2-driven population and single-cell bioluminescence rhythms. In addition, plasma immune marker concentrations and gene expression in ChP, prefrontal cortex, hippocampus and cerebellum were analyzed. cLL dampened the SCN clock but did not shorten the inactivity interval (sleep). cLD-shifts had no effect on the SCN clock, but transiently affected sleep duration and fragmentation. Both chronodisruption protocols dampened the ChP clock. Although immune markers were elevated in plasma and hippocampus, levels in ChP were unaffected, and unlike the liver clock, the ChP clock was resistant to lipopolysaccharide treatment. Importantly, both chronodisruption protocols reduced glucocorticoid signaling in ChP. The data demonstrate the high resistance of the ChP clock to inflammation, highlighting its role in protecting the brain from neuroinflammation, and on the other hand its high sensitivity to chronodisruption. Our results provide a novel link between human lifestyle-induced chronodisruption and the impairment of ChP-dependent brain homeostasis.
- MeSH
- chronická lymfatická leukemie * MeSH
- cirkadiánní hodiny * MeSH
- cirkadiánní proteiny Period genetika metabolismus MeSH
- cirkadiánní rytmus fyziologie MeSH
- lidé MeSH
- myši MeSH
- plexus chorioideus metabolismus MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Alzheimer's disease (AD) is a neurodegenerative disease often accompanied with disruption of sleep-wake cycle. The sleep-wake cycle is controlled by mechanisms involving internal timekeeping (circadian) regulation. The aim of our present pilot study was to assess the circadian system in patients with mild form of AD in their home environment. In the study, 13 elderly AD patients and 13 age-matched healthy control subjects (the patient's spouses) were enrolled. Sleep was recorded for 21 days by sleep diaries in all participants and checked by actigraphy in 4 of the AD patient/control couples. The samples of saliva and buccal mucosa were collected every 4 hours during the same 24 h-interval to detect melatonin and clock gene (PER1 and BMAL1) mRNA levels, respectively. The AD patients exhibited significantly longer inactivity interval during the 24 h and significantly higher number of daytime naps than controls. Daily profiles of melatonin levels exhibited circadian rhythms in both groups. Compared with controls, decline in amplitude of the melatonin rhythm in AD patients was not significant, however, in AD patients more melatonin profiles were dampened or had atypical waveforms. The clock genes PER1 and BMAL1 were expressed rhythmically with high amplitudes in both groups and no significant differences in phases between both groups were detected. Our results suggest moderate differences in functional state of the circadian system in patients with mild form of AD compared with healthy controls which are present in conditions of their home dwelling.
- MeSH
- aktigrafie MeSH
- Alzheimerova nemoc komplikace patofyziologie MeSH
- bydlení MeSH
- chorobopisy MeSH
- cirkadiánní proteiny Period biosyntéza genetika MeSH
- cirkadiánní rytmus fyziologie MeSH
- lidé MeSH
- melatonin analýza MeSH
- messenger RNA analýza biosyntéza MeSH
- poruchy spánku z vnitřních příčin komplikace patofyziologie MeSH
- regulace genové exprese MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sliny chemie MeSH
- studie případů a kontrol MeSH
- transkripční faktory ARNTL biosyntéza genetika MeSH
- ústní sliznice chemie MeSH
- životní prostředí MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Circadian rhythm synchronizes each body function with the environment and regulates physiology. Disruption of normal circadian rhythm alters organismal physiology and increases disease risk. Recent epidemiological data and studies in model organisms have shown that maternal circadian disruption is important for offspring health and adult phenotypes. Less is known about the role of paternal circadian rhythm for offspring health. Here, we disrupted circadian rhythm in male mice by night-restricted feeding and showed that paternal circadian disruption at conception is important for offspring feeding behavior, metabolic health, and oscillatory transcription. Mechanistically, our data suggest that the effect of paternal circadian disruption is not transferred to the offspring via the germ cells but initiated by corticosterone-based parental communication at conception and programmed during in utero development through a state of fetal growth restriction. These findings indicate paternal circadian health at conception as a newly identified determinant of offspring phenotypes.
- MeSH
- cirkadiánní rytmus * genetika MeSH
- fenotyp MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Plasma corticosterone (CORT) measures are a common procedure to detect stress responses in rodents. However, the procedure is invasive and can influence CORT levels, making it less than ideal for monitoring CORT circadian rhythms. In the current paper, we examined the applicability of a non-invasive fecal CORT metabolite measure to assess the circadian rhythm. We compared fecal CORT metabolite levels to circulating CORT levels, and analyzed change in the fecal circadian rhythm following an acute stressor (i.e. blood sampling by tail veil catheter). Fecal and blood samples were collected from male adolescent rats and analyzed for CORT metabolites and circulating CORT respectively. Fecal samples were collected hourly for 24 h before and after blood draw. On average, peak fecal CORT metabolite values occurred 7-9 h after the plasma CORT peak and time-matched fecal CORT values were well correlated with plasma CORT. As a result of the rapid blood draw, fecal production and CORT levels were altered the next day. These results indicate fecal CORT metabolite measures can be used to assess conditions that disrupt the circadian CORT rhythm, and provide a method to measure long-term changes in CORT production. This can benefit research that requires long-term glucocorticoid assessment (e.g. stress mechanisms underlying health).
- MeSH
- cirkadiánní rytmus fyziologie MeSH
- defekace fyziologie MeSH
- energetický metabolismus fyziologie MeSH
- feces MeSH
- financování organizované MeSH
- fyziologický stres fyziologie MeSH
- kortikosteron krev MeSH
- krysa rodu rattus MeSH
- pohybová aktivita fyziologie MeSH
- potkani Sprague-Dawley MeSH
- radioimunoanalýza metody MeSH
- radioizotopy jodu diagnostické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
It has been suggested that weak 50/60 Hz [extremely low frequency (ELF)] magnetic fields (MF) could affect circadian biorhythms by disrupting the clock function of cryptochromes (the "cryptochrome hypothesis," currently under study). That hypothesis is based on the premise that weak (Earth strength) static magnetic fields affect the redox balance of cryptochromes, thus possibly their signaling state as well. An appropriate method for testing this postulate could be real time or short-term study of the circadian clock function of retinal cryptochromes under exposure to the static field intensities that elicit the largest redox changes (maximal "low field" and "high field" effects, respectively) compared to zero field. Positive results might encourage further study of the cryptochrome hypothesis itself. However, they would indicate the need for performing a similar study, this time comparing the effects of only slight intensity changes (low field range) in order to explore the possible role of the proximity of metal structures and furniture as a confounder under the cryptochrome hypothesis.
- MeSH
- cirkadiánní hodiny fyziologie MeSH
- kryptochromy fyziologie MeSH
- magnetické pole * MeSH
- retina fyziologie MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH