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Development of photic entrainment of the circadian clock of the rat during early postnatal ontogenesis
Matějů, Kristýna ; Sumová, Alena (advisor) ; Höschl, Cyril (referee) ; Langmeier, Miloš (referee) ; Nevšímalová, Soňa (referee)
In most organisms, behavioral and physiological events oscillate with period ± 24 h, i.e. exhibit circadian rhythms. In mammals, circadian rhythms are generated by circadian clock within the suprachiasmatic nuclei of the hypothalamus (SCN). Light entrains circadian rhythms to the 24 h period of solar day. Information about light is conveyed from the retina to the SCN and induces expression of clock genes Period1 (Per1) and Period2 (Per2) that represent photosensitive parts of molecular circadian clockwork within SCN. Light sensitivity of Per1 and Per2 within SCN is temporally restricted to the subjective night phase. In addition, daily profiles of clock gene expression within SCN are modulated by daylenght, i. e. the photoperiod. The aim of our study was to elucidate how the mechanism of photic entrainment of the rat circadian clock develops during prenatal and early postnatal ontogenesis. Our results demonstrate that maternal circadian system provides information about external light to the fetal and early postnatal circadian clock. Circadian clock within the SCN of rat pups is light sensitive already at the first postnatal day. Mechanism gating the light sensitivity is present at postnatal day 3 and gradually maturates until postnatal day 10. The data suggest that the developing retina is responsive to...
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Hematopoietic Stem Cell Properties and Transplantation Preconditioning Studied by Competitive Repopulation of the Hematopoietic Tissue
Hlobeňová, Tereza ; Šefc, Luděk (advisor) ; Filip, Stanislav (referee) ; Langmeier, Miloš (referee)
Hemopoietic stem cells (HSCs) are primitive cells capable of replacing terminally differentiated cells throughout life. HSCs are defined as pluripotent cells able to give rise to a number of different functional cell types and they posses a huge self-renewal capability. The process during which stem cells give rise to terminally differentiated cells occurs through a number of committed progenitor cells in the bone marrow (BM) microenvironment. The place where HSCs reside in situ is called a niche. Successful bone marrow transplantation (BMT) involves homing, seeding and engraftment of HSCs in the niche. More factors, for instance chemotherapeutics and irradiation, can influence the effect of BMT. There are indices that HSCs differ between fetal and adult life. (...) The B-lymphopoiesis derived from fetal liver remained significantly less sensitive to suppression by estrogen compared to that of adult and neonatal origin. It remained its permanent feature. Exposure of HSCs to the late-stage FL microenvironment seems to be critical and mandatory for gaining later sensitivity to estrogen. Bisphophonates do not affect hematopoiesis in the mouse. They seem to be safe in regard to the effect on hematopoietic tissue in mice.
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The role of transmembrane domains in the structure and function of P2X receptors
Jindřichová, Marie ; Zemková, Hana (advisor) ; Langmeier, Miloš (referee) ; Martásek, Pavel (referee)
Purinergic P2X receptors represent a novel structural type of ligand-gated ion channels activated by extracellular ATP. So far, seven P2X receptor subunits have been found in excitable as well as non-excitable tissues. In the past ten years, the number of studies on P2X receptors has dramatically increased as investigators have begun to determine the physiological roles played by extracellular ATP and specific P2X receptor subtypes. It is already known that purinergic signaling is a key mechanism in pain sensation, brain injury, and immune processes. Little is known about their structure, mechanism of channel opening, localization and termination of ATP action by ectonucleotidases. Detailed knowledge about these events and the structure of purinergic receptor proteins evoke hope that new drugs will be developed that could prevent chronic pain and would be effective in protection against many diseases. The aim of this work is to summarize recent investigations and describe our contribution to elucidating the structure of P2X receptors. We examined the structure of transmembrane domains of the P2X4 receptor subtype, the main purinergic receptor-channel in the central nervous system, the mechanism of channel opening and closing and its sensitivity to agonists and allosteric modulator ivermectin. To...
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název v anglickém jazyce není uveden
Glogarová, Kateřina ; Syková, Eva (advisor) ; Langmeier, Miloš (referee) ; Rokyta, Richard (referee)
Magnetic resonance imaging (MRI) provides a useful noninvasive method to study the long-term migration and fate of transplanted stem cells in the central nervous system in vivo. Grafted adult as well as embryonic stem cells (ESCs) labeled with superparamagnetic nanoparticles survive in the host organism and migrate preferentially into a lesion site, where they populate the damaged nervous tissue. The migration is not affected by the route of administration; the lesion is populated with the same number of cells after intracerebral grafting as after intravenous injection. Less than 3 % of transplanted mesenchymal stem cells (MSCs) in a cortical photochemical lesion differentiated into neurons and none into astrocytes, while most ESCs (70 %) differentiated into astrocytes and only 5 % into neurons. The intravenous injection of MSCs or of the mononuclear fraction of the bone marrow, which includes hematopoietic and nonhematopoietic stem cells, progenitors and lymphocytes (BMCs), as well as the mobilization of endogenous BMCs with G-CSF (granulocyte colony stimulating factor) significantly improved the recovery of hind limb motor function and sensitivity in rats with a spinal cord compression lesion and significantly increased the spared white matter volume in the center of the lesion. The recovery was most...
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název v anglickém jazyce není uveden
Jandová, Kateřina ; Langmeier, Miloš (advisor) ; Mareš, Jan (referee) ; Hach, Petr (referee)
Hypoxia of the brain as well as the subsequent reperfusion can seriously alter the tissue microenvironment and result of the functional and structural changes of nerve and glial cells. Results of experimental studies show that some ions (e.g. Mg2+) can interfere with the brain development. To answer the question whether magnesium can modulate changes of neuronal circuits induced by hypoxia and reperfusion effect of magnesium administration on the density of nitrergic neurons (NO synthesising neurons) in the rats exposed to repeated hypoxia during the postnatal ontogeny (12, 25, and 35-day-old) was studied. NO synthesising neurons were identified according to the presence of NADPH-diaphorase (NADPH-d), the enzyme co-localized with NO synthase. Results have shown that the long-lasting intermittent hypobaric hypoxia brings about the increase of the density of NADPH-diaphorase positive neurons in all studied regions of the hippocampus in 12-day-old animals, in 25-day-old only in the hilus of the dentate gyrus, and in 35-day-old in CA1, CA3 hippocampal regions and in the ventral blade of the dentate gyrus. Contrary to that, decreased density of nitrergic neurons was found in groups of animals exposed to hypoxia till the age of 25 days in both blades of the dentate gyrus and in 35 days in the ventral blade and...
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název v anglickém jazyce není uveden
Benešová, Petra ; Langmeier, Miloš (advisor) ; Hach, Petr (referee) ; Kozler, Petr (referee)
Using hislochemical analysis (NADPH-diaphorase) we have been investigating the influence of intraperitoneal administration of kainic acid, hypoxia and combination of both these factors on neurons of the hippocampus and on the primary auditory cortex in male rats of the Wistar strain. Kainic acid was administered to 12-day-old and I8-day-old animals, which were exposed to long-lasting repeated hypoxia from the 2nd till the 17th day of age in a hypobaric chamber (for 8 hours a day). At the age of 22, 90 and 365 days, the animals were transcardially perfused with 4% paraformaldehyde under deep thiopental anesthesia. Cryostate sections were stained to identify NADPH-d positive neurons that were then quantified in CA1 and CA3 areas of the hippocampus, in the hilus, dorsal and ventral blade of the dentate gyrus and in the primary auditory cortex. In 22-day-old animals with kainic acid administered 18th day of life both hypoxia and kainic acid increased the number of NADPH-d positive neurons in the hilus, CA1 and CA3 areas of the hippocampus and in the primary auditory cortex. On the contrary, kainic acid given to the hypoxic animals lowered the number of NADPH-d positive neurons in the dentate gyrus. In 90-day-old animals with kainic acid administered 18th day of life hypoxia and kainic acid given to both,...
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