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The circadian and opioid systems are systems involved in maintaining homeostasis in the body. Disruption of the circadian system disturbs the proper timing of physiological processes, which can result in the development or exacerbation of pre-existing pathological conditions, including addiction. One of the factors that can influence the precise synchronization of the circadian system is the use and abuse of opioids. The interrelationship between the circadian and opioid systems is poorly studied. To this end, the present study investigated the effect of morphine and methadone on the rat circadian system in adulthood and during development. The aim of this dissertation was to observe the effect of acute morphine administration on the expression of clock genes in the suprachiasmatic nuclei (SCN) of adult rats, and to investigate the effect of long-term morphine or methadone administration and withdrawal on the expression of clock genes in the SCN and on the activity of the enzyme AA-NAT in the pineal gland of adult rats. Proper development of the circadian clock contributes significantly to the maintenance of health in adulthood and ensures good adaptability of the organism to changes in the external environment. No study to date has focused on examining the effects of opioid administration during...

The timing of the biological processes of organism is controlled by an endogenous circadian clock. The molecular clock is present in almost every cell and is synchronized with the external environment. The main mechanism of the clock is a transcription-translation feedback loop. The 24-hour circadian rhythm period is provided by reversible posttranslational modifications (PTMs) of the clock proteins and another regulators of the circadian clock. PTMs are further important for clock entrainment, their regulation by metabolic state in the cell, and reciprocal regulation of the circadian clock end cell cycle. Phosphorylation, histones PTMs, acetylation, SUMOylation, ubiquitination, O-linked N-acetylglucosamination and polyADP-ribosylation play a crucial role. The molecular mechanism of the biological clock is an evolutionarily conserved mechanism found in most organisms. This bachelor thesis summarizes the knowledge about the role of PTMs in the molecular mechanism of the mammalian and human circadian clocks. Key words: circadian clock, clock genes, clock proteins, posttranslational modifications

The circadian system affects almost all cells in the mammalian body. These cells include astrocytes, which together with microglia and oligodendrocytes represent the main types of glial cells found in the brain. The first chapter of this thesis presents a summary of circadian system characteristics and focuses mainly on the molecular mechanism underlying its functioning. The second chapter is devoted to astrocytes, astrocyte calcium signaling, and the process of gliotransmission. The third and last chapter connects both topics and discusses the circadian system in astrocytes. It presents evidence of astrocytic circadian oscillations existence and physiological consequences of its action. Great attention is paid to circadian rhythms in gliotransmission, with a focus on gliotransmitters ATP and glutamate. As the most impressive output of the circadian system of astrocytes is presented the participation in maintaining the rhythmic activity of the main circadian oscillator located in the suprachiasmatic nucleus of the hypothalamus. Key words: circadian system, clock genes, astrocytes, gliotransmission, calcium signaling, glutamate, ATP

The circadian system is designed to generate circadian rhythms and serve as the human inner clock. This is achieved through the molecular mechanism of autonomous transcriptional-translational feedback loops, in which so-called clock genes are involved. Circadian rhythms regulate the timing of physiological and behavioral processes, including sleep. Sleep is important for the proper functioning of the human organism. As a result of desynchronization of circadian rhythm, disturbances of sleep arise which threaten the mental and physical state of man. One of the examples is sleep deprivation which is deffined as a lack of necessary amount of sleep. Besides its negative effect on human health, there had been also reported positive effect in the treatment of symptoms in patients with unipolar depression. Other studies suggest that deprivation causes a reset of the circadian system, correcting the abnormal functioning of the internal clock. These effects have only a short duration, but it appears that they could be stabilized by combining sleep deprivation therapy with other therapeutic approaches. However, it is crucial to understand the exact mechanism that causes the positive effect in sleep deprivation therapy.

The Wnt signaling represents a highly conserved signal transduction cascade that regulates stem cell proliferation and differentiation. It plays an irreplaceable role not only during embryonic development, but also in maintaining homeostasis of adult tissues. The cell division is also influenced by the circadian clock. The clock can interact with the cell cycle either directly within a single cell or regulate it intercellularly. In order to impact surrounding cells, it uses the Wnt signaling pathway that mediates signal transduction through the extracellular space. Both Wnt signaling and the circadian clock are essential for the physiological functioning of the mammalian organism, and their disruption can lead to the development of cancer. Keywords: circadian clock, clock genes, cell cycle, Wnt signaling, cell proliferation, cancer

Circadian rhythms, which are running with a period of 24 hours, are in mammals controlled via principal clock located in the area of suprachiasmatic nuclei (SCN) and peripheral oscillators. The basic molecular mechanism governing the circadian rhythms is the transcriptional-translational feedback loop of clock genes Clock, Bmal1, Per and Cry. The CLOCK-BMAL1 protein dimer acts as an activator for the transcription of the Per and Cry genes, which retroactively inhibit this dimer and thus its own transcription. This main loop affects other genes that are involved in regulation of the core loop. The function, nuclear localization and stability of clock genes are affected by a number of postranscriptional and postranslational modifications. Sleep disorders, one of the main processes controlled by the clock genes, accompany many neuropsychiatric disorders, including autism spectrum disorder. The development of these disorders have been associated with the clock genes or their interactions with other genes that play a major role in development of these disorders.

The main topic of this thesis are changes in Circadian rhythms caused by cerebellar disorders. Mice with Lurcher mutation, which have specifically degenerated Purkinje cells layer, were choosen as animal model. Our results show that mutation of the glutamate receptor GluRδ2, which causes gradual degeneration of Purkinje cells, leads to damage of Circadian system. Mice with this mutation have reduced capability to adapt to external conditions in different light modes. They are also showing increased variability in endogenous cycle. The mice are also unable to show anticipatory behavior in time-restricted feeding. Compared to control group, affected mice do not show significant rhythm in levels of protein of Bmal1 gene in suprachiasmatic nuclei, paraventricular nuclei nor in habenula. Phosphorylated kinases ERK1/2 and GSK3ß also had distorted rhythms in suprachiasmatic nuclei. Because Circadian oscillations in locomotor activity are partly preserved, Circadian system is likely not damaged on molecular level. Cerebellar mutation hampers synchronization between suprachiasmatic nuclei of neurons and can also affect processes in the ventromedial hypothalamus regulating food intake. Our findings are the first to suggest functional interactions between cerebellum and Circadian pacemaker in suprachiasmatic...

Circadian system is a part of all living organisms. It controls suitable timing of their physiological functions and behaviour. The molecular mechanism of interlocking transcription-translational feedback loops of clock genes and their protein products forms the core of the circadian system. The main structures of this system in mammalian organisms are suprachiasmatic nuclei of the hypothalamus. Memory is also closely connected with circadian system. It is one of the most important abilities of organism for creating knowledge. Both memory and circadian system enable to the organism to adapt to changes in its external environment. The expression of clock genes was detected in brain structures involved in mediation of memory such as hippocampus, amygdale and basal ganglia. The oscillations of these clock genes influence the formation and retrieval of memory traces. The aim of this work is to summarize current knowledge about the relationship between the memory and the circadian system. Key words: circadian system, memory, clock genes, suprachiasmatic nuclei, hippocampus

In the brain, there is a center regulating circadian rhythms, which is located in the SCN. Outside these nuclei, there are other structures, which contribute significantly to coordination of circadian rhythms. Most of those nuclei are located in the hypothalamus and are connected with the SCN. These areas are involved in the management of basic physiological functions such as thermoregulation, food intake, sleep/wake cycles, hormonal secretion and control of locomotor activity. Outside the hypothalamus, there are other clocks, which work according to their location, e.g., clock in the limbic system participates in the control of cognitive functions. The olfactory lobe and retina harbor autonomous clocks that operate independently of the SCN. This work is focused on summary of the information about the selected extra- SCN oscillators in the brain their regulation of physiological functions. Key words: clock genes, circadian clocks, brain

Most of the known living organisms have developed an evolutionary adaptation to a 24-hour daily rhythm. This rhythm, known as circadian rhythm, can be preserved even in the environment, in which there is no access to light or other synchronizer. The master organ of circadian rhythm is located in the hypothalamic suprachiasmatic nucleus (SCN) and have been considered the only autonomous circadian oscillator for a long time. The new research, however, has doubted this hypothesis by showing the existence of autonomous circadian clock systems independent of SCN. One of these autonomous clocks is the circadian system in the retina. This bachelor thesis reviews current scientific knowledge on the function of mammalian retinal circadian oscillator, most importantly in the field of its localization, connection with the SCN master circadian oscillator and its influence on retinal physiology.

The mammalian circadian system is composed of major circadian pacemaker located in the hypothalamic suprachiasmatic nuclei and peripheral circadian oscillators. Molecular mechanism of interlocked transcription-translation feedback loops, as a characteristic of each circadian oscillator, results in circadian rhythms. Peripheral oscillators in other brain parts and body organs are driven by the signals from the suprachiasmatic nuclei. Some structures however generate oscillations independently from the major circadian pacemaker. The best described of them resides in the mammalian retina. The retinal circadian oscillator regulates local rhythmic synthesis of melatonin, retinal pH and photoreceptors viability. Recently, some studies occur charactering the existence of such an independent circadian oscillator also in bulbus olfactorius. For example, the olfactory bulb circadian oscillator drives olfactory sensitivity during the day. Studies about development of the mamalian circadian system have shown that the olfactory bulb circadian oscillator matures earlier than the major circadian pacemaker and represents its function during early development. Powered by TCPDF (www.tcpdf.org)

Glucocorticoids are mammalian steroid hormones secreted from the adrenal gland. The basal levels of glucocorticoids show a pronounced diurnal rhythm with maximum at the beginning of the active period and minimum at its end. Glucocorticoids have an influence over a variety of metabolic functions and their secretion is tightly regulated. This regulation also depends on the circadian system, which utilizes glucocorticoids to entrain the peripheral tissues by inducing rhythmic gene expression. The mechanisms by which glucocorticoids influence mammalian circadian system has not yet been precisely defined, especially concerning the influence of glucocorticoid signalling on gene expression in different tissues and the dynamics of glucocorticoid receptor (GR) occupancy. This thesis studies the influence of ablation of glucocorticoid signalization induced by adrenalectomy on the clock gene expression of in the central clock in the suprachiasmatic nucleus and peripheral clocks in the hippocampus and distal colon. The effect of adrenalectomy on gene expression is compared with the effect of restricting the feeding time, which has also been shown to affect glucocorticoid levels in the body. Other experiments were aimed at elucidating impact of changing the activity of GR on gene expression using synthetic GR...

The circadian system is an important coordinator of physiological functions of a mammalian organism. It comprises of a central oscillator represented by cells in the suprachiasmatic nuclei of hypothalamus (SCN) and peripheral oscillators in most if not all cells of peripheral tissues. The peripheral oscillators, similarly to the central ones, generate circadian oscillations at the level of so called clock genes and their protein products. In peripheral tissues, oscillations in expression of the individual clock genes are autonomous, however, they need to be synchronized to ensure their robust rhythmic expression. The peripheral clocks are synchronized mainly by rhythmical signals from the SCN, including signals regulating food intake. Disturbances in the clock gene expressions, as well as impaired synchronization signals, can result in various pathophysiological states. Spontaneously hypertensive rat (SHR) strain is a convenient animal model to study potential connection between the disturbed circadian system and progressive development of hypertension and metabolical diseases in mammals. Various studies have shown differences in the rhythmical expression of clock genes between SHR strain and normotensive Wistar/Wistar-Kyoto strain. The aim of this thesis is to provide insight into the early...

Circadian system enables adaptation of organisms to periodic changes in environment on the Earth. In mammals, it consists of central pacemaker in the suprachiasmatic nuclei (SCN) of hypothalamus and of oscillators that reside in other brain areas as well as in the peripheral organs and tissues. Ontogenetic development of the circadian system is a gradual process and the most dramatic changes undergo during the late embryonic and early postnatal stage. For its proper function, not only the morphological development of its individual parts, but also development of their entrainment to external environment and among each other, is important. The oscillations in clock gene expressions in the SCN occur already before birth, but in view of the fact that the levels of their protein products are undetectable, at this developmental stage, the ability of SCN to generate these oscillations in vivo has been discussed. After birth, the levels of these proteins rise and the rhythms in clock genes expression achieve the adult-like level at the postnatal age, when the synaptogenesis in the SCN is completed. The presence of a functional maternal circadian system is not necessary for the endogenous development of the SCN clock in pups, because the maternal SCN only entrains the clock and the circadian oscillations thus...

In this thesis the expression pattern of five circadian clock genes (cwo, pdp 1{$\varepsilon$}, ck 1{$\varepsilon$}, ck 2{$\beta$} and pdh) was studied in the housefly (Musca domestica). The influence of temperature on the expression pattern of these five genes and of two others genes, per and tim, was examined. The locomotor activity of flies exposed to three different temperature conditions was studied.