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Circadian system as a modulator of neuroinflammation
Kotková, Eliška ; Spišská, Veronika (advisor) ; Dočkal, Tereza (referee)
The circadian system is involved in the regulation of biological rhythms in physiological, behavioural and immune processes. These rhythms can be found in the central nervous system, including the blood-brain barrier, astrocytes, microglia, and the pineal gland, which produces the hormone melatonin. Neuroinflammation is a complex response of the central nervous system to inflammatory stimuli by rhythmic expression of pro-inflammatory and anti-inflammatory mediators or by rhythmic regulation of immune system cells. Studies have examined the influence of genes and proteins of the circadian system, suprachiasmatic nuclei, melatonin, and glial cell rhythms on neuroinflammation. Lipopolysaccharide was used to induce neuroinflammation in these studies. Based on these studies, the effect of melatonin on mikroglia and endothelial cells, and the responses of suprachiasmatic nuclei was evaluted as the most important circadian modulator of neuroinflammation. This thesis describes the basic principles of the circadian system and neuroinflammation, with the last section presenting the modulation of neuroinflammation by the circadian system. Keywords: astrocytes, blood-brain barrier, circadian system, cytokines, immune system, melatonin, microglia, neuroinflammation, suprachiasmatic nuclei
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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 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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The role of neuroinflammation in neurodegenerative CNS disease processes
Červenák, Karol ; Novotný, Jiří (advisor) ; Spišská, Veronika (referee)
Inflammatory processes in the CNS are an important element in neuroimmunity. They may be beneficial and have a neuroprotective effect but depending on the extent and duration of their activation they may also have a negative effect on the function of the CNS. Neuroinflammation is characterized by the activation of resident immune cells, microglia and astrocytes, activation of inflammatory signal pathways, recruitment of immune cells from the blood and their penetration through the blood-brain barrier. Chronic neuroinflammation may cause neurodegeneration and is key in the pathogenesis of neurodegenerative diseases. Neurodegeneration is irreversible but it can be mitigated. Therapeutic methods aimed at the modulation of neuroinflammation present a promising option for slowing down or stopping neurodegeneration for people with diseases such as Alzheimer's, Parkinson's, or Huntington's disease. The aim of this thesis is to sum up information about inflammatory processes in the brain and our current knowledge about their role in the pathogenesis of some neurodegenerative diseases. Key words: Inflammation, microglia, neurodegeneration, Alzheimer's disease, Parkinson's disease, Huntington's disease, CNS
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The effect of psychedelics on sleep
Šachová, Pavla ; Kopřivová, Jana (advisor) ; Spišská, Veronika (referee)
Recently, psychedelic drugs gain attention thanks to their potential to cure depressive disorders, anxious states or addiction. They are not causing addiction, they are not toxic and they trigger neuroplastic changes in tens of minutes or hours, which are essential for therapeutic purposes and positively correlates with an onset of antidepressant effect. Neuroplastic changes are simultaneously the connecting link between psychedelic state and sleep. In sleep the higher rate of neuroplasticity is markable during slow-wave sleep (SWS), which duration is getting shorter in patients with mental illness. The marker o neuroplasticity is slow-wave activity (SWA), which is getting higher not only in SWS, but also after intoxication with psychedelics or after long-time using of antidepressants. So the effect of psychedelics on sleep can be described as positive and inciting its therapeutical potential. The thesis is focused on ketamine which is the most recent one as for the topic of neuroplasticity and sleep.
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The monitoring of melatonin rhythm in monozygotic tweens as a marker of genetic control of circadian rhythmicity
Spišská, Veronika ; Bendová, Zdeňka (advisor) ; Svobodová, Irena (referee)
In human population, there are individual differences in the length of endogenous period which is generated by transcriptional-translational loops of clock genes in the suprachiasmatic nucleus of the hypothalamus (SCN). On the basis of these differences we divide people into the early, late or neither chronotype. Chronotypes differ from each other mainly in the rhythm of the hormone melatonin, which is used as a marker of endogenous period. They also differ in rhythm of locomotor activity. The aim of this study was to describe a difference in the phase of the circadian system in three pairs of monozygotic twins aged 8-10 years who live together and share the same daily routine. To describe these differences, we used a questionnaire CCTQ, melatonin radioimmunoassay and actigraphy. Acording to the questionnaire, one boy was determined as early chronotype (A3), one girl was determined as late chronotype (B3) and the other children were determined as neither chronotype (A2, B2, C2, C3). Among the twins there were marked differences both in the rhythm of melatonin and in the morning activity. These differences confirmed the chronotype assessed by questionnaire in the boy A3 and the girl B3. On the contrary, differences in melatonin rhythm did not confirm neither chronotype in siblings C2 and C3, and...
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Neuroprotective effects of ketamine and memantine on NMDA receptors from molecular to systemic level
Hotovec, Matěj ; Horák, Martin (advisor) ; Spišská, Veronika (referee)
The goal of this thesis is to present the evidence for the role of NMDA receptor excitotoxicity in pathology of Alzheimer's disease, epilepsy, major depressive disorder and ischemic stroke, evaluate the neuroprotective effects of NMDA receptor antagonists ketamine and memantine based on excitotoxicity research, and review the current body of evidence on their potential use as a treatment for these conditions. Keywords: excitotoxicity, ketamine, memantine, NMDAR, neurodegeneration.
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