The Dexras1 gene was identified after induction by glucocorticoid dexamethasone in pituitary tumor cells. Dexras1 has also been found in other brain regions and in the peripheral organs but its expression is rhythmic only in the suprachiasmatic nuclei of the hypothalamus (SCN), where the mammalian main circadian pacemaker is located. Dexras1 expression was also affected by stress, amphetamine or prenatal alcohol exposure. Its role in cells has not yet been explained. Dexras1 GTPase activity has been determined to be dependent on the NMDA receptor stimulation. Dexras1 acts as an activator of G protein signaling in cells. Its role has been detected in neuronal iron homeostasis or in the regulation of main circadian pacemaker sensitivity to photic and nonphotic synchronization cues during the day. The aim of our study was to describe the Dexras1 mRNA expression in the rat brain during ontogeny and during development after visual sensory deprivation by in situ hybridization. The earliest Dexras1 expression was detected on embryonic day 20, in the rat SCN and the ventral posteromedial thalamic nucleus. Postnatally, its expression also appeared in other sensory areas, motor thalamic areas, hypothalamic areas involved in the regulation of water homeostasis, or in limbic system. Our results further show...

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...

Background: Reports of subjective sleep impairments have been replicated in adults with bipolar disorder (BD) and young BD patients. Furthermore, circadian rhythm alterations are a core feature of BD. Despite the impairment in circadian rhythms and altered sleep included in various heuristic developmental models of BD, thus far, biomarkers in population at risk for BD have not been sufficiently objectively validated. Thus, we conducted: a) Explorative study of sleep and rest-activity circadian rhythm among offspring of BD parents. b) Study of sleep and rest-activity circadian rhythm among offspring of BD parents without the presence of psychopathology (except depression and anxiety disorders) based on our exploratory findings. Methods: a) 14 days of actigraphic assessment and subjective scales (Pediatric Sleep Questionnaire, PSQ; the Morningness/Eveningness Questionnaire, MEQ; and The General Behavior Inventory Sleep Subscale, GBISS) to assess circadian preference, and to identify sleep impairment symptoms. Psychopathology was assessed using psychiatric interview. b) ≥ 14 days of actigraphic assessment with advanced methods to assess the chronotype, social jet lag and sleep macrostructure, psychiatric interview and subjective psychometric scales to assess the full psychopathology profile. Results:...

This diploma thesis deals with home parenteral nutrition in the day and night regime and its effect on patients. Parenteral nutrition is usually administered at night so that patients can do normal daily activities and so that nutrition administered in this way has the least impact on their lives. Parenteral nutrition is not a physiological route of nutrient administration and it is not natural for the human body to process nutrients at night. The first part of the theoretical work presents parenteral nutrition and its composition, indications, contraindications and complications. The next part of the thesis describes home parenteral nutrition and its organisation which is necessary for this form of nutritional support to be implemented. It is necessary to monitor many laboratory values on parenteral nutrition, the theoretical part specifically mentions cholesterol, triacylglycerols, glycemia or liver function tests. One of the important parts is the chapter about circadian rhythms, hormones and metabolic changes in energy intake at night. Qualitative research was chosen for this work, which involved 17 patients on home parenteral nutrition. These patients were getting their nutrition during the night. Their laboratory values such as liver function tests, glycaemia and blood fats was evaluated and...

Many actions we observe in nature show some kind of regularity, therefore we call them rhytms. Rhytms with a period of approximately 24 hours, so called circadian rhytms, can be distinguished in many physiological processes, with the sleep-wake cycle being one of the most prominent ones. Light is the main exogenous circadian synchronizator and thanks to the circadian rhytm influence on physiological function, it's also often spoken about an influence of light on the entire organism. Nowadays, when we spend most of the day indoors under artificial light, we often suffer from a lack of natural daylight and its synchronizing potential. This is even more prominent in elderly population living in nursing homes and in other social facilities. Lately, a new type of lighting, so called biodynamic, has been introduced. Biodynamic lighting can simulate changes in natural light conditions throughout the day and therefore partially compensate for the lack of natural daylight we suffer from, and also minimize risks of the night light. In this study we aimed to test changes in the circadian system of seniors living in the Retirement Home of TGM in Beroun using questionnaires and circadian markers. We have shown a positive effect of the installed biodynamic lighting on our participants' circadian markers and...

Tryptophanis anaminoacidwhichhasmanyfunctionsinthebody. Besidesitsparticipationin theproductionofproteins,itactsasasubstrateforthekynurenineandmethoxyindolemetabolic pathways. The kynurenine pathway ends with the production of nikotinamid e adenin dinukleotide ( NAD + ) ,whichisneededfortheproductionofcellularenergy. Thus,withincreased energy demand during immune system activation, the activity of the kynurenine pathway is increased. Dueto increasedactivity,itproduces more immunoactiveandneuroactivemetab olites suchaskynurenicacidandquinolinicacid.Thesemetabolitesareinvolvedinmanyprocessesin the body and affect the pathology of many diseases. Studies show that regulation of these metabolites could be a key innovation in the treatment of cance r, cardiovascular or neurodegenerative diseases. The methoxyindole pathway is another important tryptophan processingpathway.Itsbest - knownmetabolitesareserotonin,whichactsasaneurotransmitter, andmelatonin,ahormonewithimmunomodulatoryeffect sregulatedby thecircadianclock . This workdeals with thecircadian rhythmicityofenzymeexpressionofthesetwo metabolic pathways.Italsodescribestheeffectofsystemicadministrationoflipopolysaccharideendotoxin ontheexpressionofgenesoft heseenzymes.OurexperimentsusedWistarratsat30daysofage. The lipopolysaccharide was administered...

The circadian system is a mechanism designed to generate circadian time and to synchronize it with the solar cycle. Its function is to adjust to behavioral and physiological function with the 24-hour period. The adjustment is performed using a so-called zeitgeber or synchronizer. The main circadian clock is in the suprachiasmatic nuclei (SCN) in the hypothalamus. Prolonged exposure of the organism to constant light conditions results in desynchronization of the circadian clock, which can lead to many pathologies. The impact of light at night on the organism has been studied for a long time, but the question of the impact of constant light on the development of the circadian system of the organism has been less studied. My thesis deals with this issue. Using RT-qPCR I investigated how the rhytm changes in the expression of selected clock genes in selected parts of the rat's brain, which has been kept in constant light sice birth. I also tested the impact of exposure to constant light on the early development of rhytm in locomotor activity later in the rat's life. Keywords: circadian system, photic entrainment, desynchronization under constant light, development, rat

JAK/STAT signaling pathway is one of the most studied intracellular cascades transmitting signals from the extracellular environment to the cell nucleus in order to affect expression of target genes. Circadian clocks localized in the suprachiasmatic nuclei (SCN) of the hypothalamus are sensitive especially to light but they can respond to non-photic stimuli such as growth factors, opioids, leptin and cytokines that have been demonstrated to perform its function via the JAK/STAT signaling pathway. The recent findings of our laboratory demonstrated that STAT3 protein is highly produced by SCN of rat. Primary aim of our experiments was to test the circadian regulation of STAT3 production in SCN and describe the effect of exogenously administered leptin on STAT3 phosphorylation in the SCN, pineal gland and hypothalamic structures responsible for regulated feeding behavior and energy metabolism. Because activation of leptin receptors may stimulate a number of other signaling cascades, we chose phosphorylated forms of kinase ERK1/2 and GSK-3β as other markers of intracellular changes after administration of leptin in the studied structures. Our results proved rhythmic production of STAT3 protein in SCN of rat and indicated circadian regulation of sensitivity to leptin in hypothalamic structures. The data...

There are many studies about problematic of sleep connected with shift work. However, only few studies devoted to the conditions for good rest and sleep in patients hospitalized in intensive care units. Insufficient or poor quality sleep and relaxation are the most common problems reported by patients that were hospitalized at intensive care units (ICU). Sleep is one of the basic biological needs of human. Sleep deficit can lead to psychical and psychological dysfunction that can affect the healing process. The diploma thesis is dealing with sleeping issues of patients hospitalized especially at intensive care units. The aim of the study is to determining the opinions of nurses that work at intensive care units on meeting the needs relating with sleep and rest of hospitalized patients and mapping, what interventions they use to prevent of occurrence of difficulties in this area. The theoretical part at first describes physiology of sleep and biological rhythms, then sleep disorders, then factors affecting sleep along with the consequences of the lack of sleep and last nursing process for patients with sleep disorder. The empirical part presents the results of questionnaire survey and then results of executed statistical analysis. Established hypothesis not have been assumed in results of survey...

Well functioning circadian system is crucial component of healthy organism and its disruption can result in impairment of metabolic functions with consequential development of obesity and type 2 diabetes mellitus. Obesity is in general caused by enhanced migration of pro- inflammatory polarized macrophages (M1) into adipose tissue. We have shown, that interaction of this type of macrophages with adipose tissue had significant effect on rhythmic expression of clock genes in adipocytes. We further investigated effect of high fat diet and diet enriched by omega-3 fatty acids on circadian oscillations in WAT and differently polarized macrophages. This diet affected oscillations in adipose tissue and in M0 and M2 polarized macrophages. These results support previous findings of effect of omega-3 fatty acids on metabolism and suggest their effect on circadian system as well. Key words: circadian rhythms, adipose tissue, macrophages, omega-3 fatty acids, high fat diet