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Molecular mechanism of circadian clock and its connection to neuropsychiatric disorders
Jandová, Eliška ; Sumová, Alena (advisor) ; Mašek, Tomáš (referee)
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.
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Relationship between circadian rhythms and selected biopsychosocial phenomena in healthy and clinical population
Fárková, Eva ; Kopřivová, Jana (advisor) ; Kunešová, Marie (referee) ; Sumová, Alena (referee)
Introduction: Circadian rhythms are typically manifested by individual timing of the sleep-wake cycle, expressed as a specific chronotype. Social jet-lag (SJL) is a phenomenon related to circadian preference as it reflects the phase misalignment of internal biological and external social time. SJL occurs when a person does not have the opportunity to fall asleep and get up in accordance with chronotype. Chronotype and SJL are phenomena that have recently been increasingly associated with the pathogenesis of sleep disorders and many civilization diseases, especially diseases of metabolic system. Aims and objectives: The aims of the thesis were: 1/ To determine chronotype and social jet-lag and observe further links between sex, age, BMI and other parameters in a selected sample of the Czech population across socio-demographic categories. 2/ To find out whether chronotype and the SJL play a role in the treatment of obesity. 3/ To revise the commonly used methods for chronotype assessment (questionnaires and actigraphy) for their future use in the Czech environment. Material and methods: The thesis consists of three follow-up studies (questionnaire, actigraphic and combined). Both subjective and objective methods of chronotype and SJL assessment were used in the thesis. 1) The first study was a...
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The role of Wnt signaling in interaction between circadian clock and cell cycle
Herrmannová, Terezie ; Sumová, Alena (advisor) ; Macůrková, Marie (referee)
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
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Molecular mechanisms of mammalian circadian clocks, its sensitivity to constant light and aging
Novosadová, Zuzana ; Sumová, Alena (advisor) ; Doležel, David (referee) ; Mráz, Miloš (referee)
Many processes in mammalian body exhibit circadian rhythms. These rhythms are driven by an intricate system composed of the central pacemaker, suprachiasmatic nuclei (SCN) in the brain, which entrains the peripheral oscillators in various organs, such as pancreas, liver, colon and lungs. Circadian clocks are autonomously driven in each cell based on molecular circuits involving so called clock genes, such as BMAL, CLOCK, PER and CRY. Age- dependent impairment of physiological functions of mammalian body, such as behaviour and metabolic functions, has been well documented. However, it has not been fully elucidated whether the impairment is linked with worsening of the circadian clock function. The aim of our study was to find out whether i) aging affects basic properties of the circadian clock in SCN and peripheral organs, such as pancreas, colon, liver and lungs, ii) aging- induced changes in glucose homeostasis affect the properties of the circadian clock in the pancreas, and iii) the sensitivity of circadian clock in SCN and peripheral organs to disturbances in environmental lightning conditions is altered during aging. We used groups of adult (9 months) and aged (25 months) animals which were subjected to 3 different light regimes, namely to light/dark regime (LD 12:12), constant light (LL) and...
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Chronotype, daily regime and its relationship with socio-demographic characteristics and life style
Cápíková, Markéta ; Sumová, Alena (advisor) ; Sedláčková, Markéta (referee)
This diploma thesis focuses of czech population's description from the perspective of chronotype and its relationship to sociodemographic characteristics and to variables affecting lifestyle. The aim of this thesis is to describe the sample examined in terms of social jetlag. The thesis is based mainly on quantitative methods, specifically I was using individual forms of regression analyzes, which allow to capture the influence of independent variables on the dependent variable. The analytical part data from Qualitas 2016 survey within the AV21 Strategy project are processed. The analysis revealed the existence of an association between chronotype and gender, respectively between chronotype and age. It also turned out that extreme owls consume addictive substances to a greater extent than extreme larks. Owls also generally have higher BMI, lower psychological well-being and more often suffer from social jetlag than those with early circadian preference. However, the social jetlag does not only concern respondents with late circadian preference, but the whole sample analyzed. The average length of social jetlag in the sample is 66 minutes. The analysis also revealed the link between social jetlag and addictive substance abuse.
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Synchronization of circadian clock in rat during ontogenesis and in adulthood
Olejníková, Lucie ; Sumová, Alena (advisor) ; Šlamberová, Romana (referee) ; Mareš, Jan (referee)
The circadian system temporally controls behavioral and physiological processes in most organisms so that they change during the day and night with a period of about 24 h. It is an evolutionary adaptation to anticipate periodic changes in environment on the Earth. In mammals, the circadian system consists of the central pacemaker in the suprachiasmatic nuclei (SCN) of hypothalamus and of oscillators located in numerous peripheral organs and tissues. At the molecular level, the circadian clock is based on the rhythmic expression of so called clock genes. The ontogenetic development of the circadian system is a gradual process and the most important changes undergo during the late embryonic and early postnatal stage. Many behavioral, hormonal and metabolic signals provided by the mother are considered to be involved in circadian clock synchronization during early ontogenesis. The mechanisms of the entrainment are not fully known yet. The aim of this thesis was to study the development of the circadian clock and its entrainment via maternal signals and to compare the development of circadian rhythms in two model rat strains - Wistar rat and spontaneously hypertensive rat (SHR). Firstly, we described the ontogenetic maturation of the Wistar rat circadian clock in the colon from the fetal stage until...
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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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