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The effect of long-term morphine application on clock genes expression in the rat brain
Pačesová, Dominika ; Bendová, Zdeňka (advisor) ; Roubalová, Lenka (referee) ; Polidarová, Lenka (referee)
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...
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Circadian system in bulbus olfactorius
Kyclerová, Hana ; Bendová, Zdeňka (advisor) ; Polidarová, Lenka (referee)
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)
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Modulation of the JAK/STAT signaling pathway in the suprachiasmatic nucleus of rat hypothalamus
Moravcová, Simona ; Novotný, Jiří (advisor) ; Krulová, Magdaléna (referee) ; Polidarová, Lenka (referee)
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...
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Molekulární mechanismus cirkadiánních hodin a jejich synchronizace v trávicím systému potkana
Polidarová, Lenka ; Sumová, Alena (advisor) ; Doležel, David (referee) ; Zeman, Michal (referee)
The circadian system controls the timing of behavioral and physiological processes in most organisms with a period of about 24 h. In mammals, the circadian system consists of the central oscillator in the suprachiasmatic nuclei (SCN) and peripheral oscillators located in numerous organs such as the liver, heart, lung, muscles, intestines etc. Peripheral oscillators are cell-autonomous, they could also work independently of the SCN entrained by a feeding cycle. The misalignment of the endogenous timekeeping system, due to e.g. irregular daily schedule or shiftwork, may lead to the development of severe diseases including sleep disorders, gastrointestinal (GI) problems and various types of cancer. Therefore, understanding the molecular mechanism of the circadian clock may facilitate the treatment of diseases caused by malfunction of the circadian system. In my PhD thesis, I focused on the determination and synchronization of circadian clocks within the rat digestive system and on their development during ontogenesis. Moreover, the circadian system of a rat strain with pathology, i.e., spontaneously hypertensive rat (SHR) was also studied. We identified the circadian clocks in the individual parts of the intestine and ascertained that these clocks are mutually synchronized with the phase-delay along...
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Circadian system in bulbus olfactorius
Kyclerová, Hana ; Bendová, Zdeňka (advisor) ; Polidarová, Lenka (referee)
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)
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Clock genes in mammalian circadian pacemaker
Cimerová, Veronika ; Bendová, Zdeňka (advisor) ; Polidarová, Lenka (referee)
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...
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Mammalian circadian clock in peripheral organs, molecular mechanism and entrainment
Polidarová, Lenka ; Kuthan, Martin (referee) ; Sumová, Alena (advisor)
Mammalian circadian clock in peripheral organs, molecular mechanism and entrainment The circadian system controls timing of behavioral and physiological processes in most organisms. In mammals, central oscillator is located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. Apart from the SCN, peripheral oscillators are located in numerous organs like liver, heart, lung, muscle, intestine etc. The central and peripheral oscillators need to be synchronized by external cues (Zeitgeber). The SCN coordinates and entrains the phase of the clocks in numerous peripheral tissues via neuronal and humoral signals. For the SCN, dominant synchronizer is external light-dark cycle. Peripheral oscillators are cell-autonomous, they could work also independently of the SCN as a consequence of a feeding cycle. The basic molecular core clock mechanism responsible for generating circadian rhythms in the central and peripheral clocks is composed of transcriptional/translational feedback loops between the clock genes and their protein products. The aim of the present thesis was to ascertain whether the clock gene and protein expressions exhibit circadian rhythms in the rat intestine and whether the core clock mechanism drives expression of a cell cycle regulator rWee1. Next aim was to reveal how the circadian...
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