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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...

Circadian clock in the suprachiasmatic nucleus of the hypothalamus (SCN) regulates daily rhythms in behavior and physiology and is an important part of the mechanisms regulating mammalian homeostasis. SCN are synchronized with a 24hour cycle mainly by light, but they can also be regulated by a variety of nonphotic signals, such as growth factors, opioids, cytokines, or lipopolysaccharide (LPS), which act by inducing the JAK/STAT signaling pathway. STAT family proteins (i.e. signal transducers and activator of transcription) regulate many aspects of cellular physiology, from growth and differentiation to immune response. However, the JAK/STAT signaling pathway has not yet been studied in the SCN and the function of STAT proteins in the SCN has not yet been clarified. In the first part of the thesis, we focused on localization of STAT3 and STAT5 proteins in the rat SCN and determination of rhythm in proteins and mRNA. Our experiments showed the daily rhythm in the levels of STAT3 protein in SCN astrocytes of rat with low but significant amplitude and with maximum in the morning. In addition, we revealed strong but nonrhythmic expression of STAT5A protein in astrocytes and STAT5B protein in nonastrocytic cells of SCN. It was also found that Stat3 mRNA show, similarly to protein, circadian rhythm in...

Circadian rhythmicity, which evolved in accordance with the rhythmicity of the external environment tied to the earth's rotation, governs the regular rhythms of our physiology and behavior. The central circadian clock in the suprachiasmatic nuclei of the hypothalamus controls the roughly 24-hour rhythmicity of many peripheral clocks of most cells of the body, that can be observed from the molecular to the behavioral level. The intrinsic circadian period (τ) in humans is on average slightly longer than 24 h, but may also be slightly shorter. Individuals with a short τ are referred to as morning chronotypes, whereas individuals with a long τ are referred to as evening chronotypes. However, the majority of the population belongs to the so-called intermediate chronotype. The molecular mechanism of circadian oscillations controlled by the circadian clock has been shown to be closely linked to cellular metabolism. Many physiological processes important for physical and cognitive performance are also regulated by the circadian system. The main aim of both studies was to quantify the difference in performance during morning and evening testing in subjects of a pronounced evening and morning chronotype. While the motivation for conducting Study A was practical, with the aim of identifying potential biases...

Circadian clock in the suprachiasmatic nucleus of the hypothalamus (SCN) regulates daily rhythms in behavior and physiology and is an important part of the mechanisms regulating mammalian homeostasis. SCN are synchronized with a 24hour cycle mainly by light, but they can also be regulated by a variety of nonphotic signals, such as growth factors, opioids, cytokines, or lipopolysaccharide (LPS), which act by inducing the JAK/STAT signaling pathway. STAT family proteins (i.e. signal transducers and activator of transcription) regulate many aspects of cellular physiology, from growth and differentiation to immune response. However, the JAK/STAT signaling pathway has not yet been studied in the SCN and the function of STAT proteins in the SCN has not yet been clarified. In the first part of the thesis, we focused on localization of STAT3 and STAT5 proteins in the rat SCN and determination of rhythm in proteins and mRNA. Our experiments showed the daily rhythm in the levels of STAT3 protein in SCN astrocytes of rat with low but significant amplitude and with maximum in the morning. In addition, we revealed strong but nonrhythmic expression of STAT5A protein in astrocytes and STAT5B protein in nonastrocytic cells of SCN. It was also found that Stat3 mRNA show, similarly to protein, circadian rhythm in...

Long-term exposure to constant light results in desynchronization of the circadian system in an adult and is associated with reduced efficiency of many physiological functions timed to the exact time of day, or with the development of some of the so-called civilization diseases. Constant light in adults also results in deterioration of the cognitive abilities or changes in the sleep structure. The effect of night light on the health of an adult organism is studied mainly in connection with shift work or with light pollution. The question of what effect the increased level of night light has on the development of the organism, especially on the development of the nervous system and the circadian system itself, is less studied. This diploma thesis focused on the identification of the extent of changes in the expression of Per2, Nr1d1, Stat3, BDNF genes, as well as genes encoding NMDA receptor subunits and some tissue-specific genes in the retina. Our experiments were performed on adult Long-Evans rats, that spent the first 20 days of their postnatal development in low-intensity constant light. Changes in expression were determined by quantification of mRNA by RT-qPCR in the structures of the frontal and parietal cortex, olfactory bulb, hippocampus, suprachiasmatic nucleus and retina. Behavioral tests...

The circadian clock exists in every organism and their period is approximately 24 hours. This circadian rhythm is maintained even in a completely non-periodic environment but must be adapted to a precise 24-hour solar cycle using a synchronizer, called zeitgeber. The main controlling organ of the circadian rhythm are the suprachiasmatic nuclei (SCN) in the ventral hypothalamus. There are also peripheral clocks, for example in the liver or lungs. These peripheral clocks operate autonomously but the SCNs synchronize them with their own period and phase. The most important zeitgeber is the light and dark alternation. This bachelor thesis describes the consequences of conditions where there is no regular light and dark alternation and constant light conditions are established instead. Constant light can disturb the circadian rhythm and desynchronize the circadian clocks. This bachelor thesis summarizes the scientific knowledge of desynchronization by the effect of constant light and briefly describes the selected pathologies resulting from the desynchronization of the circadian system. Selected pathologies include ovarian tumour and breast cancer, obesity and insulin resistance, immunosenescense and schizophrenia. Key words constant light, circadian system, suprachiasmatic nucleus

The rhythm of ATP accumulation is an one of examples of circadian rhythmicity which is demonstrated across the animal kingdom. It is located in the suprachiasmatic nucleus of hypothalamus, which is a centre of circadian clock and imposes rhytmicity on a whole organism. The question concering the ATP rhythm in an organotypic culture and the impact of melatonin on it has been discussing in this thesis. The synthesis of melatonin is regulated by the activity of the SCN and the hormon itself is known for its feedback on the SCN and a capability of regulating it. It has been shown that ATP rhythm is significantly inhibited under the constant control of melatonin and this inhibition is dose-dependent on a scale of 0,1-10 nM. In case of one-time applied melatonin in 4 p.m. there is no reduction in the accumulation of extracellular ATP but there is a phase shift in ATP rhythm. It has also been shown that ATP rhythm is inhibited and desynchronized under the control of tetrodotoxin which blocks an electric activity of neurons. These results show that melatonin is capable of inducing phase delay of ATP rhythm in SCN and reducing an amount of extracellular ATP, that the effect of melatonin is probably mediated by specific receptors and lastly that ATP rhythm is a result of cell-cell interaction between neurons...

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

Bipolar affective disorder is a serious psychiatric disease with prevalence of about 1% in general population. Typical symptoms are mood changes: manic periods are followed by depressions, with possible asymptomatic period of variable duration between them. It alters patient's everyday life and often leads to suicidal tendencies. Bipolar disorder is related to impaired circadian rhytms that are regulated from suprachiasmatic nuclei in hypothalamus. Impaired circadian rhytms in bipolar disorder are manifested by abnormalities of sleep and daily activity and by disrupted circadian secretion of several hormons. One of many factors that link bipolar disorder to circadian system at molecular level is the function of voltage-dependent calcium channels of L-type. Expression of these channels is regulated by the clock genes and their proper function is important for maintaining endogenous oscillations in the main oscillator located in suprachiasmatic nuclei. A common finding in patients with bipolar disorder is polymorphism of the gene for 1 subunit of the Cav1.2 channel. Abnormal function of calcium channels, consequent to the polymorphism, may be one of the causes that alter circadian rhytms in bipolar disorder. Key words: circadian system, suprachiasmatic nucleus, bipolar disorder, L-type calcium...

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)

The behavior of mammals and their physiological processes are dependent on the daily rhythms. These rhythms are controlled by an endogenous circadian clock that responds to light/dark cycles of environment. In mammals, the circadian clocks, are arranged hierarchically, and work in almost all cells and tissues. Suprachiasmatic nuclei (SCN) in the hypothalamus are at the top of the hierarchy and work as a major circadian pacemaker. This work presents the clock genes that have been discovered in the last twenty years in the SCN of mammals. The first chapter focuses on the general mechanism of circadian rhythms and structure of the SCN. The second chapter describes the transcriptional-translational feedback loops that are an essential part of the proper function of the circadian clock, and function of individual genes is briefly introduced in this chapter. The following chapters already include a chronological characterization of Clock, Bmal1, Period and Cryptochrome genes, as they were discovered. If the clock gene expresses different function from the clockwork mechanism, it is briefly introduced in the final paragraph on the chapter. The final chapters deal with other molecules, casein kinases, ROR and REV-ERB receptors that affect its function expression and degradation of circadian genes in the...