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Polydendrocytes and their role in CNS
Suchá, Petra ; Anděrová, Miroslava (advisor) ; Tvrdoňová, Vendula (referee)
Polydendrocytes (NG2+ cells) are recently discovered glial cells in central nervous system (CNS) distinct from neurons, oligodendrocytes, astrocytes and microglia. Polydendrocytes could be identified mainly by the expression of the proteoglycan NG2 and platelet derived growth factor receptor alpha. They could be found in grey and white matter and represent the largest proliferating cell population in adult CNS. It is accepted that a subpopulation of polydendrocytes gives rise to oligodendrocytes not only in development, but also in adult CNS and after demyelination. A subpopulation gives rise also to protoplasmic astrocytes in embryonic development. In in vitro studies was observed that neurons and astrocytes may arise from polydendrocytes. Electrophysiological studies revealed that polydendrocytes form synapses with neurons and that their rate of proliferation could be controlled this way. Polydendrocytes are very important in study of remyelination after ischemia and demyelinating diseases, as they might serve as source of new oligodendrocytes or possibly of another glial cells. This thesis summaries general knowledge about polydendrocytes. Initially, I focus on their immunohistochemical markers and morphology. Next, I summarise findings about their development and fate in both embryonic and adult CNS. A...
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Physiological and pathological potential of astroglial NMDA receptors
Džamba, Dávid ; Anděrová, Miroslava (advisor) ; Vyklický, Ladislav (referee) ; Paleček, Jiří (referee)
Cortical glial cells contain both ionotropic and metabotropic glutamate receptors. Despite several efforts, a comprehensive analysis of the entire family of glutamate receptors and their subunits present in glial cells is still missing. Here, we provide an overall picture of the gene expression of ionotropic (AMPA, kainate, NMDA) and the main metabotropic glutamate receptors in cortical glial cells isolated from GFAP/EGFP mice during ageing as well as before and after focal cerebral ischemia. Employing single-cell RT-qPCR, we detected the expression of genes encoding subunits of glutamate receptors in cortical GFAP/EGFP- positive (GFAP/EGFP+ ) glial cells. Most of the analyzed cells expressed mRNA for glutamate receptor subunits, the expression of which, in most cases, even increased after ischemic injury. Data analyses disclosed several classes of GFAP/EGFP+ glial cells with respect to glutamate receptors and revealed in what manner their expression correlates with the expression of glial markers prior to and after ischemia. Furthermore, we also examined the protein expression and functional significance of NMDA receptors in glial cells. Immunohistochemical analyses of all seven NMDA receptor subunits provided direct evidence that the GluN3A subunit is present in GFAP/EGFP+ glial cells and that...
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Early morphogenesis of lower cheek teeth in mice with gene defects.
Lagronová, Svatava ; Peterková, Renata (advisor) ; Anděrová, Miroslava (referee) ; Buchtová, Marcela (referee)
Tooth number is reduced in humans and mice when compared to the presumed basic tooth formula in mammals. In the regions, where teeth had been suppressed during evolution, a supernumerary tooth can appear as a result of abnormal development. However development of a supernumerary tooth, as well as origin of other anomalies, cannot be directly investigated in human embryos. That is the development of a supernumerary tooth was studied in a mouse model of this anomaly. The aims of the thesis were focused to verifying the hypothesis: Development of the supernumerary tooth in mutant mice is based on the revitalization of the rudimentary primordia of the teeth suppressed during evolution. We compared the morphological and quantitative aspects of the developing epithelium of the largest rudimentary (premolar) tooth primordia, called MS and R2, in the mandibles of WT, Spry2-/- , Spry4-/- , Spry2-/- ;Spry4-/- and Tabby mutant mice. Similarly, the upper incisor in WT mice was analysed and compared to the development of the duplicated incisor in Spry2+/- ;Spry4-/- mutant mice. In comparison to controls, decreased cell apoptosis and increased cell proliferation together with an enlarged volume of the dental epithelium were found during rudimentary tooth development in Spry mutant mice. These changes showed the...
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Neurogeneze a gliogeneze v dospělém mozku po ischemickém poškození
Honsa, Pavel ; Anděrová, Miroslava (advisor) ; Vyklický, Ladislav (referee) ; Mazurová, Yvona (referee)
Ischemic brain injury belongs to the most common cause of death in the developed countries. High complexity of this disorder significantly slows and limits the possible treatment. Currently, there is only one treatment available - the application of the thrombolytic, tissue plasminogen activator, while thousands of other drugs failed during clinical testing. Great expectations were seen in the stroke treatment employing neural stem cells obtained from several external sources; nevertheless, low survival rate, limited favorable outcome and enormous ethical issues complicate the application of such therapy. On the other hand, in the adult mammalian brain exist two endogenous processes - neurogenesis and gliogenesis. These processes need to be fully described and understood, in order to employ them as a source of new cells after injury. Therefore, this thesis focuses on the processes of adult neurogenesis and gliogenesis predominantly after ischemia. Adult neurogenesis and gliogenesis are processes, by which neurons or glial cells are generated from stem/progenitor cells. Both these processes are strongly influenced by brain injury; nevertheless, their contribution to regeneration after ischemia in the human brain is negligible. Here, we aimed to describe the role of polydendrocytes in the...
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Induction of neurogenesis and gliogenesis after ischemic CNS injury - the role of Wnt signaling pathway
Koleničová, Denisa ; Anděrová, Miroslava (advisor) ; Nerandžič, Vladimír (referee)
This bachelor thesis is focused on ischemic injury of the central nervous system (CNS), one of the most frequent causes of death and disability in the world, and its possible treatment via the induction of neurogenesis. It consists of three different parts. In the first part, main neurogenic regions of the CNS, the subventricular zone and gyrus dentatus (GD) of the hippocampus, are described at the cellular, as well as molecular level. The second part is mainly dedicated to ischemic injury, to the global and focal brain ischemia. A particular chapter of this part describes changes in neurogenesis and gliogenesis after ischemic injury of the brain, changes in the induction of radial glial cells, proliferation and migration of neural progenitor cells and neuroblasts. In this chapter, we also describe the activation of astrocytes, microglia and NG2 glia (also known as polydendrocytes) after ischemic injury of the CNS. The last, third part of the bachelor thesis, is focused on signaling pathways, which significantly influence neurogenesis: Shh (Sonic hedgehog homolog), Notch and Wnt (Wingles/Integrated) signaling pathways. Special attention is devoted to the Wnt signaling pathway, which is an essential part of molecular mechanisms in nerve cells. Keywords: neurogenesis, gliogenesis, hippocampus, gyrus...
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Calcium signalling in glial cells in progress of Alzheimer disease
Waloschková, Eliška ; Anděrová, Miroslava (advisor) ; Maršáková, Lenka (referee)
Alzheimer's disease (AD) is a neurodegenerative disorder affecting the entire central nervous system including glial cells. The mechanisms of this disease are not yet entirely clear, although recent studies suggest that among the known hallmarks of AD, such as accumulation of amyloid β and hyperphosphorylated tau, dysregulation of intracellular calcium homeostasis is proposed to be a significant feature both in neurons and glial cells, namely astrocytes and microglia. Glial cells play an important role both in healthy brain and during AD progression. Their major functions, such as supporting neurons or maintaining synapses, are impaired during this disease. Recent findings suggest that aberrant glial calcium signaling activated during AD, could possibly promote the malfunction of these cells and increase their inflammatory response, thus affecting neurons and causing brain damage. It is likely, that the ongoing inflammation and the impaired calcium signaling affect one another, consequently enhancing the progression of AD.
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Nervous tissue regeneration following ischemic injury in adulthood - the role of glial cells
Kamenická, Monika ; Anděrová, Miroslava (advisor) ; Kletečková, Lenka (referee)
Ischemic stroke (ischemia) is one of the most common causes of death in the world. The consequences of this disease are enormous and markedly affect the lives of patients who often are unable to live a full quality of life as before. Therefore, the current research is focused on elucidating new mechanisms that could mitigate the effects of ischemia and better regeneration of nerve tissue. This theses aims to summarize the current knowledge about neurogenesis/gliogenesis in the nerve tissue under physiological conditions, after ischemic injury and subsequent regeneration. The first chapter is focused on neurogenesis in the nervous tissue of adults. The two main neurogenic regions are described, such as subventricular zone and the gyrus dentatus in hippocampus. The following is a brief description of cells that are located in neurogenic regions and their function under physiological conditions. The second chapter focuses on gliogenesis in adult nervous tissue and describes the glial cells responsible for numerous functions in CNS. Furthermore, the functions of individual types of glial cells are listed. The third chapter gives the overview about pathophysiology of ischemia. The author tries to explain what is happening in the brain tissue during and following ischemia, what types of ischemia are...
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Astrocyte volume regulation during aging
Eliášová, Barbora ; Anděrová, Miroslava (advisor) ; Vargová, Lýdia (referee)
Astrocytes, as one of the glial cell types, have many important functions in healthy functioning of the central nervous system (CNS) but also in its pathology. Since they play a key role in maintenance of ionic, neurotransmitter and water homeostasis in CNS, they possess the ability to regulate their volume. Hypo- or hyperosmotic stress can trigger regulatory volume decrease or increase in astrocytes in order to stabilize their volume. During aging, astrocytes undergo many changes together with the rest of the brain. In order to determine whether these alterations involve also regulatory volume mechanisms, we employed three dimensional morphometry, which comprises confocal microscope scanning of fluorescently labelled astrocytes in brain slices of EGFP/GFAP mice and quantification of astrocyte volume during different pathological stimuli. Time-dependent volume changes of hippocampal astrocytes were recorded while applying either hypoosmotic solution or solution with high extracellular potassium concentration. In the four different age groups studied in the experiment, several differences in volume changes were discovered together with some sex-dependent alterations in astrocyte volume. Additionally, in accordance with previous studies, two subpopulation of astrocytes were identified using...
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Expression and functional characteriz ation of transient receptor potential vanilloid - related channel 4 (TRPV4) in hippocampal astrocytes after ischemia /reperfusion
Butenko, Olena ; Anděrová, Miroslava (advisor) ; Bojar, Martin (referee) ; Vlachová, Viktorie (referee)
The polymodal transient receptor potential vanilloid 4 (TRPV4) channel, a member of the TRP channel family, is a calcium-permeable cationic channel that is gated by cell swelling, low pH and high temperature may be involved in neuronal and glia pathophysiology. In the present study, we examined the impact of cerebral hypoxia/ischemia (H/I) on the functional expression of astrocytic TRPV4 channels in the adult rat hippocampal CA1 region. Hypoxia/ischemia was induced by a bilateral 15-minute occlusion of the common carotids combined with hypoxic conditions. Our immunohistochemical analyses revealed that 7 days after H/I, the expression of TRPV4 is markedly enhanced in hippocampal astrocytes of the CA1 region and that the increasing TRPV4 expression coincides with the development of astrogliosis. Adult hippocampal astrocytes in slices or cultured hippocampal astrocytes respond to the TRPV4 activator 4-alpha-phorbol-12,-13-didecanoate (4αPDD) by an increase in intracellular calcium and the activation of a cationic current, both of which are abolished by the removal of extracellular calcium or exposure to TRP antagonists, such as Ruthenium Red or RN1734. Following hypoxic/ischemic injury, the responses of astrocytes to 4αPDD are significantly augmented. Collectively, we show that TRPV4 channels are...
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Glial cells and their role in Alzheimer disease
Eliášová, Barbora ; Anděrová, Miroslava (advisor) ; Kazantsev, Dmitry (referee)
Alzheimer's disease is a neurodegenerative disorder, affecting mostly elderly people. It causes memory impairment and modifies the ability to talk, learn and make decisions. These are gradually getting worse until the patient loses them completely. Alzheimer's is the most common form of dementia worldwide, however until these days there is no cure. The main reason for this is that mechanisms and causes of this disease are still not utterly understood. Besides the neurodegeneration caused by aggregation of βamyloid protein and hyperphosphorylated tau protein, glial cells of central nervous system play also important role in the Alzheimer's disease. Astrocytes, microglia, oligodendrocytes and recently discovered synantocytes ensure various functions necessary for correct functioning of the brain and damage of these cells can be fatal. During a neurodegenerative disorder such as Alzheimer's, they are able to improve the course of the disease but also do the contrary and aggravate it by malfunctioning or losing one or even more of their functions. Key words: Alzheimer's disease, β amyloid, tau protein, astrocytes, microglia, oligodendrocytes, synantocytes
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