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Developmental changes in expression levels of the chosen subunits of NMDA and AMPA receptors and action of their antagonists on physiological and epileptic phenomena
Szczurowska, Ewa Katarzyna ; Mareš, Pavel (advisor) ; Rokyta, Richard (referee) ; Bendová, Zdeňka (referee)
During early stages of postnatal development, glutamate receptors of NMDA and AMPA type, undergo intensive functional changes due to modifications of their subunit composition (Pachernegg et al., 2012: Paoletti et al., 2013). The NR2B-containing NMDARs (NR2B/NMDARs) and GluA2-lacking AMPARs (Ca 2+ -permeable) that are highly expressed in immature brain, are implicated in increased excitability, seizures generation, excitotoxicity, and neuronal death (Vizi et al., 2013). Pharmacological blockade of these types of receptors by their specific antagonists, can exhibit anticonvulsant effects at early stages of postnatal development. Therefore, we tested the influence of the IEM1460, a specific antagonist of Ca 2+ -permeable AMPARs and the Ro 25-6981 maleate, a highly selective and activity-dependent antagonist of NR2B/NMDARs on physiological excitability and epileptic phenomena induced in immature rats. Anticonvulsant action of IEM1460 was tested in two models of epileptic seizures: pentylenetetrazol (PTZ)- induced convulsions and cortical afterdischarges (ADs), induced in animals at P12, P18 and P25. Our results indicate that the effects of IEM1460 on various types of seizures depend on their sites of origin in the brain, developmental stage, and GluA2 subunit expression profile. To clarify the action...
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Characteristics of the nervous system of mice with a Lurcher mutation
Boubín, Josef ; Bendová, Zdeňka (advisor) ; Tůma, Jan (referee)
The glutamate receptor δ 2 (GluRδ2) is expressed in dendrites of Purkinje cells localized in the cerebellar cortex. Correct function of GluRδ2 is necessary for cerebellar development, synapse formation between parallel fibers of the granular and Purkinje cells and for inducing long term depression important in memory formation. Lurcher mutation, localized to 6th autosomal chromosome, transforms GluRδ2 into constitutively open ion channel by amino acid substitution in third transmembrane domain. As a result, almost complete disappearance of Purkinje cells population and a large degeneration of granular cells and olivary neurons occurs. Mice impaired by Lurcher mutation have lower body weight and reduced litter size. Fertility of males is not affected. Lurcher mutants display extensive behavioral deficits. Mice suffer from ataxia typical for cerebellar neurodegenerations. They have reduced physical performance, impaired spatial orientation and learning capabilities. The aim of this work is to summarize recent knowledge about Lurcher mutation from molecular basis to behavioral manifestation. Specific characteristics of this degeneration allow us to investigate influences of neurodegenerative cerebellar disorders on cognitive functions of the brain as a whole, study causing factors and treatment...
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The disruption of the circadian system in bipolar disorder and its association with the polymorphism of L-type calcium channel
Filipovská, Eva ; Bendová, Zdeňka (advisor) ; Novosadová, Zuzana (referee)
Bipolar affective disorder is a serious psychiatric disease with prevalence of about 1% in general population. Typical symptoms are mood changes: manic periods are followed by depressions, with possible asymptomatic period of variable duration between them. It alters patient's everyday life and often leads to suicidal tendencies. Bipolar disorder is related to impaired circadian rhytms that are regulated from suprachiasmatic nuclei in hypothalamus. Impaired circadian rhytms in bipolar disorder are manifested by abnormalities of sleep and daily activity and by disrupted circadian secretion of several hormons. One of many factors that link bipolar disorder to circadian system at molecular level is the function of voltage-dependent calcium channels of L-type. Expression of these channels is regulated by the clock genes and their proper function is important for maintaining endogenous oscillations in the main oscillator located in suprachiasmatic nuclei. A common finding in patients with bipolar disorder is polymorphism of the gene for 1 subunit of the Cav1.2 channel. Abnormal function of calcium channels, consequent to the polymorphism, may be one of the causes that alter circadian rhytms in bipolar disorder. Key words: circadian system, suprachiasmatic nucleus, bipolar disorder, L-type calcium...
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CIrcadian regulation of miRNA and clock-controlled genes in tumorigenesis
Balounová, Kateřina ; Pácha, Jiří (advisor) ; Bendová, Zdeňka (referee)
The circadian clock generates circadian rhythms, which participate on regulation of a number of signalling pathways. Disruption of the circadian regulatory mechanism is linked to a development and a progression of certain types of cancer including colorectal tumorigenesis. Progression of tumorigenesis depends on the cell cycle machinery related to cell proliferation and apoptosis. MiRNAs play a role in initiation and progression of tumorigenesis because they interfere in regulatory pathways associated with tumorigenesis. The aim of the thesis was to determinate existence of circadian rhytms in clock controlled genes (Tef, Dbp), miRNAs (miR-1-3p, miR-16-5p, miR-34a-5p, miR-155-5p, miR-192-3p) and genes of the cell cycle machinery (Ccnd1, Ccne1, Ccna1, Ccnb1) and apoptosis (Casp3, Bcl2, Bad). Further, to compare detected circadian rhythms during aging and neoplastic transformation of colon by quantitative RT-PCR. We have observed circadian expression of Tef, Dbp, Ccne1, Ccna1, Ccnb1, Casp3 and Bcl2 in young mice colon, Tef, Dbp, miR-1-3p, Ccne1, Ccna1 in old mice colon and Tef and Dbp in colorectal tumors. In summary, circadian expression of clock controlled genes varied but was maintained in mice colorectal tumors. In aging we demonstrated weakening of circadian rhythms of the genes of the cell...
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The relationship between circadian system and cell cycle
Vrtílková, Andrea ; Bendová, Zdeňka (advisor) ; Fárková, Eva (referee)
The circadian system is able to oscillate by itself owing to the transcriptional-translation feedback loop. Components of this loop do not affect just their own run, but they also have an impact on some other functions of the cell, for example cell cycle. This interaction is made by clock proteins (PER, CRY etc.) and by clock-controlled proteins (WEE1, TIM, XPA etc.). These proteins participate in the cell cycle run and have an impact on check-points. Disruption of the circadian clock can cause faults in cell cycle check-points, storing of DNA damages and increased cell apoptosis or tumor progression. Key words: circadian systém, cell cycle, WEE1, XPA, P21, C-Myc, TIM, PER
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Circadian system of the retina
Kozel, Tomáš ; Bendová, Zdeňka (advisor) ; Moravcová, Simona (referee)
Most of the known living organisms have developed an evolutionary adaptation to a 24-hour daily rhythm. This rhythm, known as circadian rhythm, can be preserved even in the environment, in which there is no access to light or other synchronizer. The master organ of circadian rhythm is located in the hypothalamic suprachiasmatic nucleus (SCN) and have been considered the only autonomous circadian oscillator for a long time. The new research, however, has doubted this hypothesis by showing the existence of autonomous circadian clock systems independent of SCN. One of these autonomous clocks is the circadian system in the retina. This bachelor thesis reviews current scientific knowledge on the function of mammalian retinal circadian oscillator, most importantly in the field of its localization, connection with the SCN master circadian oscillator and its influence on retinal physiology.
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Circadian system and memmory
Skálová, Kateřina ; Bendová, Zdeňka (advisor) ; Houdek, Pavel (referee)
Circadian system is a part of all living organisms. It controls suitable timing of their physiological functions and behaviour. The molecular mechanism of interlocking transcription-translational feedback loops of clock genes and their protein products forms the core of the circadian system. The main structures of this system in mammalian organisms are suprachiasmatic nuclei of the hypothalamus. Memory is also closely connected with circadian system. It is one of the most important abilities of organism for creating knowledge. Both memory and circadian system enable to the organism to adapt to changes in its external environment. The expression of clock genes was detected in brain structures involved in mediation of memory such as hippocampus, amygdale and basal ganglia. The oscillations of these clock genes influence the formation and retrieval of memory traces. The aim of this work is to summarize current knowledge about the relationship between the memory and the circadian system. Key words: circadian system, memory, clock genes, suprachiasmatic nuclei, hippocampus
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The photoperiodism and hibernation
Pařezová, Lucie ; Bendová, Zdeňka (advisor) ; Weissová, Kamila (referee)
Many organisms living in seasonal environments use annual changes in the length of the day for timing of their responses, such as reproduction, migration or hibernation. Hibernation allows animals to survive difficult periods associated particularly with cold temperatures and lack of food resources. This adaptation requires many physiological, morphological and behavioral changes. Some of these changes take longer, so their right timing is crucial. For most hibernators in temperate regions shortening of the photoperiod is the most reliable signal for initiation of these changes. This work describes the transduction of photoperiodic information to the melatonin signal, its effects in the pars tuberalis and the significance of this structure in seasonal physiology. A more detailed description is devoted to hibernation, and in the last chapter there is briefly mentioned photoperiodism in nonhibernating organisms. Powered by TCPDF (www.tcpdf.org)
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Circadian principle of human chronotype
Ševčíková, Kateřina ; Bendová, Zdeňka (advisor) ; Šmotek, Michal (referee)
Circadian system is an oscillating system with approximately 24 hour period. In humans, it consists of suprachiasmatic nuclei and peripheral oscillators. Suprachiasmatic nuclei by means of external stimuli synchronize its endogenous period about the time of day. It is controlled by clock genes. The circadian system affects hormone levels, and with the homeostatic system is the major regulator of sleep. In these cyclic systems in humans, there are some differences that define human chronotype. This thesis is focused on the changes in the circadian system that underlie human chronotype. It deals with polymorphisms of clock genes, periods of the rhythms in the production of hormones such as melatonin and cortisol and their differences in distinct chronotypes. At the circadian chronotypes, there were also found differences in REM and REM sleep cycles and their amplitudes. Chronotype and circadian system are dependent on age and gender. Powered by TCPDF (www.tcpdf.org)
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Circadian regulation of STAT3 protein in the SCN and it's activation by leptin in the SCN, other parts of hypothalamus and the pineal gland
Moníková, Veronika ; Bendová, Zdeňka (advisor) ; Jelínková, Dana (referee)
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...
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