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Synchronization of circadian system during prenatal and early postnatal development
Houdek, Pavel ; Sumová, Alena (advisor) ; Novotná, Růžena (referee)
One of the few attributes common to almost all living organisms is an ability to generate and maintain endogenous rhythms, which are controlled by a biological clock. The processes, which recur with a period of about 24 hours, are known as the circadian rhythms. The circadian clock controls rhythms of molecular, physiological as well as behavioral processes and adapts their activity to regularly appearing changes in day and night or season. In case of mammals, central oscillator is located in the hypothalamic suprachiasmatic nuclei (SCN). The SCN clock entrains rhythms of peripheral oscillators located in cells of other tissues. The central oscillator itself is synchronized with external environment mainly by a light-dark cycle, however, other cues can entrain the SCN clock as well. For example, during prenatal development, entrainment of a fetal clock is entirely dependent on non-photic cues derived from maternal organism. This study aimed to investigate a mechanism of the communication between the maternal and fetal central oscillators. A hypothesis was tested whether maternal melatonin may play a role in entrainment of the circadian clock in the fetal SCN. Furthermore, a mechanism, how melatonin may entrain the fetal clock was investigated at molecular level. The results provided evidence, that...
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Photoperiodic entraiment of circadian clock in suprachiasmatic nucleus
Parkanová, Daniela ; Sumová, Alena (advisor) ; Vopálenský, Václav (referee)
Most of physiological processes run in the organisms persistently, they begin in a definite rhythm again and again. The greatest attention is paid to the rhythms, whose period is equal to one day - they are called circadian rhythms. In case of mammals, these circadian rhythms are under control of the central circadian clock that resides in the suprachiasmatic nucleus, a part of the anterior hypothalamus. The mechanism of rhythm generation is based on interacting transcriptional-translational feedback loops that control expression of the clock genes in every single cell. Clock-controlled genes transmit these rhythms into the whole organism where they drive many physiological processes. Clock genes are expressed also in the peripheral oscillators (for example in liver, lungs, heart) and are under direct control of the central oscillator. Circadian clock needs to be entrained everyday to the external time to function precisely. The main entraining cue is the light part of the day. The length of the light part of the day, i.e. photoperiod, changes during the year rapidly in our latitudes and the central oscillator has to adapt to the changes all the time. The length of the photoperiod is encoded directly in the central oscillator by the transcriptional-translational relations among the clock genes and...
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Circadian regulation of sleep during ontogenesis in humans
Grieblová, Adéla ; Sumová, Alena (advisor) ; Soták, Matúš (referee)
The circadian system has evolved as an adaptation to periodically changing conditions on Earth. In mammals, and therefore in humans, the circadian system consists of the central and perip- heral oscillators generating a circadian rhythm. One of the most significant process exhibiting circadian rhythm is the sleep-wake cycle. Sleep is regulated by cooperation of circadian and homeostatic process. There are changes in circadian regulation of sleep during ontogenesis in human. The changes mainly releate to chronotype, i.e., to the diurnal preferences of activity and sleep. In the first years of life, there is a typical morning chronotype. In the end of first decade of life, the circadian phase begins to delay and reaches its maximal eveningness during ado- lescence. In adulthood, the preference changes again toward morning chronotype and reaches extreme morningness in elderly. Changes in circadian regulation of sleep during ontogenesis depend not only on age, but also on sex. 1
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Circadian system in patients with Alzheimer's disease
Weissová, Kamila ; Sumová, Alena (advisor) ; Stuchlík, Aleš (referee)
Alzheimer's disease (AD) is a severe neurodegenerative disease that primarily affects the elderly population. Recently, epidemiological studies have pointed to significant increase in the disease cases within the world population, and therefore, it is important to pay more attention to it. The most distinctive symptom of AD is an impairment of memory, especially its episodic component. Apart from this, sleep-wake rhythm disturbance is also very burdensome symptom of this disease. An increasing sleep fragmentation during the night and an increasing number of naps during the day in AD patients represents one of the biggest complications for home caregivers. Therefore, sleep problems are one of the most common reasons for a permanent hospitalization of patients with AD. Apart from these difficulties for the patient's surroundings, the irregular and altered sleep-wake rhythm has also many negative physiological impacts on the patient's health. The alternation in sleep and waking follows a prominent daily rhythm. The sleep-wake rhythm is driven by a circadian system and, therefore, the episodes of sleep and waking regularly alternate with approximately 24h period even in a non-periodic environment. Master circadian clock is located in the suprachiasmatic nucleus of hypothalamus (SCN). SCN is an...
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Impact of circadian system disruption on development of gastrointestinal disorders
Kubištová, Aneta ; Sumová, Alena (advisor) ; Červená, Kateřina (referee)
The ability to sense 24-hour cycles in external environment and to adapt to them is present in a great array of species living on the Earth. Mammals possess internal time-keeping system which is composed of circadian clocks located in the suprachiasmatic nuclei (SCN) of the hypotalamus and peripheral clocks in various tissues and organs of the body. These clocks are adapting to the changes of external environment, such as light and dark cycles or feeding cycles. Peripheral clocks in the organs of the digestive system are synchronized with the signals derived from the central clock in the SCN and also with signals from food intake. Discordance between these signals may result in development of various diseases of the gastrointestinal tract (GIT) related to insufficient digestion or even in higher risk of developing a cancer. This bachelor thesis is generally aimed at circadian rhythms in the body, with the focus on rhythms in the GIT. It will deal with the importance of the circadian rhythms for correct GIT functions. Furthermore, the thesis is focused on connection between the desynchonization of the circadian clock and GIT disease development, namely of obesity and cancer.
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Circadian clock in the hippocampus
Liška, Karolína ; Sumová, Alena (advisor) ; Riljak, Vladimír (referee) ; Ježek, Karel (referee)
To adapt to the daily changing environment, living organisms on Earth have developed an inner clock. In mammals, the clocks are organized in a circadian system which is governed by the central oscillator in suprachiasmatic nuclei (SCN) and consists of peripheral oscillators located in tissues and organs throughout the body. The synchrony of the entire system allows proper alignment of physiological processes to the optimal time of day. It was shown that cognitive performance and memory formation are also subjected to daily variations and many brain regions involved in these processes, especially hippocampus (HPC), were recently found to harbor circadian clocks. Nevertheless, the precise function of these clocks and the mechanism of their synchronization to the external conditions remain to be elucidated. The focus of my PhD thesis was a detailed analysis of the circadian clocks in rodent HPC. We aimed to characterize the oscillators in distinct HPC subregions, identify signals responsible for their synchronization and compare the HPC clock properties to those of the clock in the choroid plexus (CP) which is the adjacent non-neuronal structure. Moreover, we examined the role of clocks in HPC and other brain regions in the process of memory formation, focusing on time memory acquisition. First, we...
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Dynamic of PER2 clock protein degradation detected by real time bioluminescence assay in the tissue explant of the circadian clock of mPER2Luc mouse
Stanislavová, Faustýna ; Sumová, Alena (advisor) ; Doležel, David (referee)
Suprachiasmatic nuclei are the main oscillator of circadian rhythms. Using clock genes and their protein products (forming transcription-translation feedback loops), suprachiasmatic nuclei play an important role in the control of many physiological functions. Bioluminescence (the amount of hourly protein PER2) was measured by a method using transgenic organisms. In this work, cycloheximide was used to inhibit proteosynthesis and to subsequently monitor the degradation of PER2 in real time. The protein was then measured in explants of suprachiasmatic nuclei of adult mice, in suprachiasmatic nuclei of fetuses and in placentas. Furthermore, the effects of glycogen synthasykinase 3b inhibitors on the dynamics of PER2 protein degradation were compared. A selective inhibitor CHIR-99021 and a non-specific inhibitor lithium chloride were used. The experiment shows that the CHIR inhibitor slows down protein degradation in all tissues used. In contrast, the effect of a non-specific lithium chloride inhibitor has not been clearly demonstrated. In fetal nuclei, its effect on the dynamics of degradation was slowing, while in adult nuclei, degradation was significantly accelerated. No significant results were observed in placental explants. Research focusing on the influence of these clock genes, respectively...
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Molecular mechanisms of entrainment of the fetal circadian clocks
Lužná, Vendula ; Sumová, Alena (advisor) ; Šauman, Ivo (referee) ; Štaud, František (referee)
In order to adapt to changing external conditions, organisms developed the endogenous biological clock for predicting daily alterations. This so-called circadian system drives functions and processes in the whole body with an approximately 24h period. The central oscillator, located in hypothalamic suprachiasmatic nuclei (SCN), is synchronized by light and subsequently sends the information about the time of the day to the rest of the body. Even in the ontogenesis, the functional SCN clock is crucial for proper development as well as health later in life. Since the maturation of embryonic SCN is not completed before birth, maternal signals seem to play a fundamental role in setting and synchronizing the fetal clock. During my PhD studies, we focused on elucidating the nature of maternal signals and their diverse impact on fetal SCN of rat and mouse models. We have revealed that developing SCN is able to sense distinct signals related to various maternal behavioral regimes. Importantly, we have discovered eminent role of glucocorticoids in synchronizing the fetal SCN, along with their ability to accelerate SCN development. These observations point out the importance of regular daily routine and noxious effect of stress during pregnancy. Since the mother communicates with the fetus through placenta...
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Other factors influencing daytime melatonin levels.
Rácz, Beáta ; Vondra, Karel (advisor) ; Kršek, Michal (referee) ; Sumová, Alena (referee)
Circadian rhythms are important for the adaptation of the organism to the changes of the environment. The internal biological clock (pacemaker) has a rhythm which is slightly longer or shorter than 24 hours. Melatonin is a pineal hormone produced during the dark period. The gastrointestinal tract is the main extrapineal source and the main source of melatonin during the light period. There are missing studies which are focused on the effects of the food on steroid hormones. Aim: To elucidate the effect of the food on selected hormone levels in two consequent studies of eight healthy nonsmoker premenopausal women in follicular phase of their menstrual cycle. Results: 1) 16 hours long monitoring: The levels of melatonin decreased significantly two hours after lunch. Cortisol levels were decreasing throughout the whole day and an additional decrease was found two hours after lunch. We were the first to report the significant connections of estradiol and SHBG to food intake. 2) Monitoring after different stimuli: Levels of melatonin increased 40 minutes after the i.v. application of glucose. In oGTT this increase was slower. Cortisol has decreased after the application of glucose, more apparently after its i.v. application. The breakfast led to increase of cortisol levels. OGTT and i.v.GTT caused some...
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