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Calcium signalling in astrocytes under physiological and pathological conditions
Svatoňová, Petra ; Anděrová, Miroslava (advisor) ; Kolář, David (referee)
Calcium signalling in astrocytes represents an important component, which enables proper neuronal functioning under physiological conditions. Alterations in Ca2+ signalling, accompanied by an increase in intracellular calcium levels is a hallmark for numerous pathological states of central nervous system, such as traumatic and ischemic brain/spinal cord injuries, epilepsy as well as neurodegenerative diseases, such as Alzheimer's disease and psychiatric disorders, such as schizophrenia. The research analyzing the molecular components of astrocytic Ca2+ signalling can help us understand the control mechanisms used in calcium signalling and thus be greatly beneficial for further therapeutic research. Powered by TCPDF (www.tcpdf.org)
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Proliferation and differentiation of NG2-glia following ischemic brain injuries
Kirdajová, Denisa ; Anděrová, Miroslava (advisor) ; Machová Urdzíková, Lucia (referee)
NG2-glia, a fourth major glial cell population, were shown to posses wide proliferation and differentiation potential in vitro and in vivo, therefore the aim of this study was to compare the rate of proliferation and differentiation potential of NG2-glia after different types of brain injuries, such as global and focal cerebral ischemia (GCI, FCI) or stab wound (SW), as well as during aging. Moreover, we aimed to determine the role of Sonic hedgehog (Shh) in NG2-glia proliferation/differentiation after FCI. We used transgenic mice, in which tamoxifen triggers the expression of red fluorescent protein (tdTomato) in NG2-glia and cells derived therefrom. Proliferation and differentiation potential of tdTomato+ cells in sham operated animals (controls) and those after injury were determined by immunohistochemistry employing antibodies against proliferating cell nuclear antigen and glial fibrillary acidic protein. FCI was induced by middle cerebral artery occlusion, GCI by carotid occlusion with hypotension and SW by sagittal cortical cut. Shh signaling in vivo was activated or inhibited by Smoothened agonist or Cyclopamine, respectively. Compared to controls, the proliferation rate of tdTomato+ cells was increased after all types of injuries, while it declined in aged mice (15-18- months-old) after...
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Changes in neuroglia in degenerative disorders of the central nervous system
Kirdajová, Denisa ; Zach, Petr (advisor) ; Hock, Miroslav (referee)
Neurodegenerative diseases are a serious disorders of the central nervous system characterized by neuronal loss with a subsequent damage of the brain. This damage may have diverse consequences like a gradual loss of memory and intellect, problems with musculoskeletal system and not least death. Causes of these diseases are not yet fully understood. In addition to neurons neuroglia also plays an important role in these diseases of the central nervous system. In neurodegenerative diseases are astrocytes, oligodendrocytes, microglia and NG2 cells involved in their many aspects. They participate in the protective as well as in the detrimental aspect of these diseases. This work, therefore, presents an overview of previously acquired knowledge of neuroglia in various types of degenerative disorders of the CNS (Alzheimer`s disease, Parkinson`s disease, amyotrophic lateral sclerosis, multiple sclerosis, Wernicke encephalopathy, HIV associated dementia, frontotemporal dementia, vascular dementia). Powered by TCPDF (www.tcpdf.org)
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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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Role of glial cells in the immune response of mice infected by neurotropic fluke Trichobilharzia regenti
Macháček, Tomáš ; Panská, Lucie (advisor) ; Kopecký, Jan (referee)
A central nervous system (CNS) can be invaded by plenty of parasites, including parasitic helminths. Host's immune response during such infections includes not only participation of peripheral lymphocytes, but also astrocytes and microglia, resident glial cells present in the CNS. Activation of astrocytes and microglia has been recently demonstrated also in mice infected by neurotropic avian trematode Trichobilharzia regenti (Digenea: Schistosomatidae) for which mammals represent accidental hosts. The parasite does not mature in them and elicits development of inflammatory reaction in the CNS which may take part in parasite's destruction. Employing in vitro experiments, this thesis aimed at evaluation of the possible role of astrocytes and microglia in murine immune response to T. regenti. For this purpose, primary astrocyte and microglia culture preparations were established and the cells were then stimulated by antigens of T. regenti (homogenate of transformed cercariae, recombinant cathepsins B1.1 and B2). After that, production of nitric oxide and proinflammatory cytokines (IL-1 beta, IL-6, TNF-alpha) was measured. The results revealed that in vitro stimulated astrocytes and microglia increase production of nitric oxide, IL-6 and TNF-alpha. Such response to parasite's antigens could influence...
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Single cells gene expression profiling and analysis
Novosadová, Vendula ; Kubista, Mikael (advisor) ; Beneš, Vladimír (referee) ; Vopálenský, Václav (referee)
Cells are the basic units of life. Studying complex tissues and whole organs requires an understanding of cell heterogeneity and responses to stimuli at the single-cell level. Even the cells, which belong to the same cell type, behave differently at a specific moment and contain different amount of mRNA. Quantitative polymerase chain reaction (qPCR) is one the most sensitive methods for the detection of mRNA, however, gene expression profiling in single cells leads to a large amount of missing data due to the fact that the transcript is missing, or is below the level of detection. Therefore, it is necessary to establish a new statistical approach for analysis of single cells. In this thesis the potential of single-cell gene expression profiling using the high throughput instrument Biomark, focusing on data analysis and biological interpretation, is discussed. Data normalization and handling of missing data are two important steps in data analysis that are performed differently at the single-cell level. Single cells are not normalized by reference genes but the number of cells as a normalizer is applied. Missing data are replaced by value, which is equaled one quarter of transcript amount in the cell. Furthermore it is shown how single-cell gene expression data can be viewed and how subpopulations...
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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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Host immune response in neuroinfections caused by parasitic helminths.
Macháček, Tomáš ; Panská, Lucie (advisor) ; Štáfková, Jitka (referee)
Among helmiths, there are some parasites which may dwell in the central nervous system of humans during their ontogenic development. Contrary to the former concept of so called immune privilege of this site, hosts develop the immune response against them. Both immune cells and resident immunocompetent cells (astrocytes, microglia) participate in these immune reactions. The host immune response consists of cellular as well as humoral immunity. This bachelor's thesis gives the general features of the immune response in the central nervous system and describes the immune response during particular helminthic neuroinfections: neuroschistosomiasis, neurocysticercosis and neurotoxocarosis.
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