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The role of orexins in food intake and chosen pathological phenomena
Zelená, Anna ; Sumová, Alena (advisor) ; Balounová, Kateřina (referee)
Orexins are neuropeptides produced in the lateral hypothalamus in the brain and peripheral organs. These neuropeptides are essential in regulating arousal and energy balance. They also participate in the reward system and secure water homeostasis. Orexins bind to the orexin receptors differently expressed in various tissues. The binding of orexins to their receptors couples with downstream signalling pathways, e.g., Ca2+ , diacylglycerol and protein kinase C pathways. Low concentration of adenosine triphosphate leads to the inactivation of orexin-expressing neurons and the reduction of energy expenditure. On the contrary, high intracellular concertation of adenosine triphosphate activates energy expenditure. Food intake is regulated by orexins and glucose, sirtuin 1, forkhead box transcription factor 2, and leptin. This thesis aims to find connections between the role of orexins in regulating food intake and the development of some pathological phenomena, e.g., hypertension, obesity, and anorexia nervosa. Keywords orexin, obesity, anorexia nervosa, glucose, insulin, stress
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Synchronization of circadian clock in hippocampus
Kubátová, Eliška ; Sumová, Alena (advisor) ; Liška, Karolína (referee)
Circadian rhythms refer to the physiological, biochemical and behavioral changes of the organism with a period of about 24 hours, such as the cycle of sleep and wakefulness, the release of hormones, enzymatic activity or gene expression. Apart from the central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, we find many other peripheral oscillators in which we observe the rhythmic expression of clock genes. In this study, we focused on one of the peripheral brain oscillators located in the hippocampus. The hippocampus is best known for its role in memory formation through the mechanism of long- term potentiation (LTP). The formation of LTP is another process that exhibits circadian variation. Although the rhythmic expression of genes in the hippocampus has already been demonstrated, the mechanisms of synchronization of these clocks remain a subject of investigation. In this study, we studied the effect of candidate substances - N-methyl-D- aspartate (NMDA) and leptin on the circadian clock of the hippocampus. Genetically modified mPer2Luc mice were used as a model. The main goal of the work was to introduce a method of preparing organotypic explants of the hippocampus of these mice for monitoring the circadian clock in real time using the LumiCycle device. Next goal was...
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Circadian regulation of digestive system function and its disturbances due to external factors
Běloušková, Klára ; Sumová, Alena (advisor) ; Balounová, Kateřina (referee)
Circadian clocks regulate the behavior of cells in living organisms in 24hour periods. They react to environmental influences and, by synchronizing with them, ensure optimal cell function and the overall health of the organism. Biological clocks in the gastrointestinal tract and their functions can be influenced by several factors, including the timing of food intake or the influence of the microbiome. The correct timing of food intake can be essential in maintaining the functional physiology of the organism as well as the appropriate composition of the gut microbiome. Disruption of the synchronization between these factors and the biological clock in the gastrointestinal tract leads to disharmony of the organism, its improper function and the development of disease. The timing of food intake and the cultivation of an appropriate microbiome is critical to maintaining optimal health and should not be neglected by the public.
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Hormonal synchronization of fetal circadian clocks in suprachiasmatic nuclei
Kapsdorferová, Viktória ; Sumová, Alena (advisor) ; Sehadová, Hana (referee)
Rhythmic non-light maternal signals, such as various behavioral, neurohumoral or metabolic factors, may play a key role in synchronization of the fetal circadian clock. This diploma thesis focuses more closely on the possible role of leptin and dopamine in the hormonal synchronization of the fetal central clock resides in the suprachiasmatic nuclei of the hypothalamus. A transgenic mouse fetus, which has luciferase fused to the clock gene Period 2, was used as an experimental model. This allowed us to monitor the operation of the fetal central clock in real time by recording the bioluminescence of tissue explants. Exogenous administration of dopamine during the decline in bioluminescence at normalized circadian time 15 induces larger phase delays compared to vehicle. Leptin, on the other hand, can participate in the development of spontaneous rhythms by stabilizing the integrity of the circadian rhythm, manifested by slowing down the rhythm dampening. At the level of individual cellular oscillators, significant regional differences in amplitude and period were not observed using bioluminescence microscopy. However, a slight dispersion of cell phases was observed after administration of dopamine during decreasing bioluminescence. In the case of leptin, there was a prolongation of period of the cell...
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Circadian rhythms in adipocytes and impact of their disruption
Zavřelová, Michaela ; Sumová, Alena (advisor) ; Spišská, Veronika (referee)
This bachelor thesis deals with circadian rhythms in adipocytes and the consequences of their disruption. The thesis summarizes current scientific knowledge and explores the mechanism of rhythm control at the molecular level, which is formed by transcriptional translational feedback loops. Adipocytes control lipid metabolism through the production of adipokines, adipogenesis, lipogenesis, and lipolysis. The research focuses on how clock genes are involved in these processes. All of these events, which are characteristic of adipocytes, are highly regulated and the genes that are involved in them are transcriptionally activated by clock gene proteins. Circadian rhythms are an integral part of our lives, and desynchronization of rhythms between the main oscillator, which is the suprachiasmatic nuclei, and peripheral adipocytes can lead to metabolic disorders, which in turn can lead to obesity, insulin resistance, or type 2 diabetes. Obesity is one of the biggest problems of modern society, and disrupted circadian rhythms due to today's lifestyle are one of the causes of its development. Key words: circadian rhythms, clock genes, adipocytes, obesity, PPARγ, adipogenesis, lipogenesis, lipolysis, leptin, adiponectin
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Effect of antidepressants on placental monoamine homeostasis
Horáčková, Hana ; Štaud, František (advisor) ; Sumová, Alena (referee) ; Soukup, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Kralove Department of Pharmacology and Toxicology Candidate: Mgr. Hana Horackova Supervisor: prof. PharmDr. Frantisek Staud, Ph.D. Title of doctoral thesis: Effect of antidepressants on placental monoamine homeostasis Depression in pregnancy is an increasingly common problem and it is reported that up to 25 % of pregnant women suffer from depression and approximately 13 % are prescribed antidepressants. Currently, the most commonly prescribed antidepressants in pregnancy are selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). However, the safety of these treatments is still controversial, as poor pregnancy outcomes such as organ malformations, increased incidence of neurological disorders, and preeclampsia have been reported in pregnant women taking antidepressants. However, knowledge of the responsible mechanisms is still lacking at present as they have not been sufficiently investigated. Although the effect of antidepressants on the availability of serotonin (5-HT), dopamine (DA) and norepinephrine in brain tissue has been extensively characterized in the literature, the interactions of antidepressants with placental monoamine transporters have not received attention to date. However,...
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Neuroprotective effects of novel anorexigenic analogs of prolactin-releasing peptide (PrRP) in models of neurodegeneration in vitro and in vivo
Mengr, Anna ; Maletínská, Lenka (advisor) ; Sumová, Alena (referee) ; Hampl, Aleš (referee)
Alzheimer's disease (AD) is a progressive brain disorder characterized by extracellular beta amyloid (Aβ) plaques, intracellular neurofibrillary tangles formed by hyperphosphorylated Tau protein and neuroinflammation. Since obesity and type 2 diabetes mellitus (T2DM) have been established as risk factors for the development of neurological disorders, anorexigenic and antidiabetic peptides, such as prolactin-releasing peptide (PrRP) seem to be potential neuroprotective agents. In the first part of the study, the molecular mechanisms of action of natural PrRP31 and its lipidized analog palm11 -PrRP31 was studied in the human neuroblastoma cell line SH-SY5Y. Both compounds significantly activated the signaling pathways typical for insulin promoting cell survival and growth. Moreover, PrRP31 and palm11 -PrRP31 increased cell viability and suppressed apoptosis in methylglyoxal-stressed SH-SY5Y cells. The second part of the thesis was focused on the neuroprotective and anti-inflammatory effects of 2-month-long subcutaneous administration of palm11 -PrRP31 in the brains of APP/PS1 mice, model of Aβ pathology. Palm11 -PrRP31 significantly reduced the Aβ plaque load and microgliosis in the hippocampi, cortices, and cerebella. Furthermore, palm11 -PrRP31 increased the synaptogenesis and attenuated...
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Rhythmic function of placenta and the impact of disruption in maternal-placental-fetal axis
Světlíková, Nela ; Sumová, Alena (advisor) ; Pačesová, Dominika (referee)
In mammals, the circadian rhythms result of a complex endogenous system consisting of hierarchically organized oscillators. The system enables the synchronization of the organism's internal processes with the external environment. It consists of the main component, the central clock, located in the suprachiasmatic nuclei in the hypothalamus, and peripheral clocks in other cells, tissues and organs. The placenta is a temporary, specialized mammalian organ that is part of the mother-placenta-fetus axis and exhibits rhythmicity in its functions. The aim of this thesis is to summarize the rhythmic functions of the placenta, such as immunity, protection, and production of hormones and other mediators that play an important role in fetal development and pregnancy. In addition, the thesis also describes rhythmic changes, that occur during pregnancy in the mother-placenta-fetus axis and how these rhythms influence each other. Keywords Placenta, circadian clock, ontogenesis, fetus, maternal synchronization, hormones, enzymes, immunity
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Effect of maternal obesity on postnatal development of circadian clocks
Sejrková, Veronika ; Sumová, Alena (advisor) ; Spišská, Veronika (referee)
This thesis focuses on the synchronizing effect of obesity in mothers on ontogenesis of the circadian system in their offspring during gestation and postnatal life. Additionally, the work summarizes its impact on health of offspring in adulthood. During postnatal life, the central clock oscillator (SCN) is synchronized with external conditions through alternating period of light and darkness, but during prenatal ontogenesis of the main oscillator and peripheral oscillators, the SCN is synchronized with maternal signals, both behavioral, metabolic and hormonal. In the event of disruption of the maternal circadian and metabolic systems due to obesity, the circadian clocks of the offspring are incorrectly synchronized during gestation and breastfeeding, which may have a long-term effect on their health later during postnatal life. Maternal obesity is considered the main trigger for obesity occurring later.
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