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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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NMDA receptors in astrocytes: their role in ischemic brain injury
Valný, Martin ; Anděrová, Miroslava (advisor) ; Hock, Miroslav (referee)
Glutamate is the main excitatory neurotransmitter in the mammalian brain, and its transmission is responsible for higher brain functions, such as learning, memory and cognition. Glutamate action is mediated by variety of glutamate receptors, of which N-methyl-D-aspartate (NMDA) receptors are the most remarkable due to their high Ca2+ permeability and complex pharmacology. Despite the widespread expression of NMDA receptors in astroglial cells in different brain regions, they have been studied mostly in neurons. Therefore, the role of astroglial NMDA receptors under physiological conditions as well as in pathological states, such as cerebral ischemia, is not fully understood. The aim of this work was to elucidate the presence, composition and function of these receptors in astrocytes under physiological conditions and after focal cerebral ischemia. For this purpose, we used transgenic (GFAP/EGFP) mice, in which astrocytes express enhanced green fluorescent protein (EGFP) under the control of human promotor for glial fibrillary acidic protein (GFAP) enabling astrocyte isolation and their collection via fluorescence-activated cell sorting. We performed single-cell RT-qPCR analysis of astrocytes isolated from the cortex of adult mice. The analyzed cells were isolated from the uninjured brains of 50...
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Neurogenesis and gliogenesis after ischemic brain injury in EGFP/GFAP mice
Dlouhá, Veronika ; Anděrová, Miroslava (advisor) ; Vargová, Lýdia (referee)
Focal ischemia induces enhancement of neurogenesis/gliogenesis in the subventricular zone (SVZ) of the lateral ventricle and it also leads to glial scar formation in the vicinity of the ischemic lesion. The gliotic scar is mainly formed by reactive astrocytes that express glial fibrilarly acidic protein (GFAP), nevertheless this protein is also expressed in adult multipotent neural stem cells (NSCs). Therefore, we have used the strain of transgenic mice (GFAP/EGFP mice), in which the enhanced green fluorescent protein (EGFP) is expressed under human GFAP promoter in astrocytes as well as in NSCs, thus allowing us an immediate vizualization of these cells, and to estimate the effect of ischemic injury on their fate during proliferation and differentiation in vitro. Focal ischemia was induced by the occlusion of the middle cerebral artery (MCAO) and 3 days post injury, an immunohistochemical analysis was carried out. Furthermore, the cell isolation from SVZ and the region of gliotic scar was performed, followed by their cultivation under proliferative conditions (as neurospheres) and their differentiation for 7-10 days. The differentiation potential of these cells was studied using immunocytochemical analyses and patch clamp technique was employed to estimate their membrane properties. Based on increased...
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Developmental dynamic of vestigial tooth primordia and possibilities for its experimental influencing
Procházka, Jan ; Peterková, Renata (advisor) ; Černý, Robert (referee) ; Anděrová, Miroslava (referee)
Tooth development in the mouse embryo is an important model of developmental biology for studying not only odontogenesis, but also general organogenesis, and it also has considerable biomedical potential. Tooth shares many developmental features with other epithelial organs whose development initiates from budding of epithelium. The tooth is not only an isolated organ, but it is a part of the organ system - dentition. During dentition development, there is serial initiation of developing teeth. The presumed basic tooth formula in placental mammals comprised three incisors, one canine, four premolars and three molars. Dentition of rodents is already very derived being only formed by one continuously growing incisor and three molars in each dental quadrant. In place of missing teeth between the incisor and molars is a toothless region called diastema. During mouse embryonic development, it is possible to observe the initiation of development of rudimentary tooth primordia in both incisor area and in prospective diastema. In contrast to these morphological findings, the generally accepted assumption is that only the prospective functional incisor and the first molar (M1) develop during initial stages of mouse odontogenesis (ED 11-14) and, consequently, all the molecular signalling events are...
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Morphological characteristics of alterations in the striatum induced by neurodegenerative process in the brain
Němečková, Ivana ; Mazurová, Yvona (advisor) ; Anděrová, Miroslava (referee) ; Martínek, Jindřich (referee)
("Morphological characteristics of alterations in the striatum induced by neurodegenerative process in the brain") Huntington's disease (HD) is an inherited neurodegenerative disorder. Although the cause of HD, i.e. the production of the mutant form of unstable protein huntingtin (mhtt) which contains 40 and more CAG repeats is known, the effective therapy is not yet available. Therefore, the use of animal models is crucial for the study of the pathogenesis of this fatal disorder. To date, there is no suitable experimental model simulating the neurodegenerative process (NDP) developing in the striatum of the human HD brain. Most of rodent models of HD fall into two broad categories - the neurotoxic lesions and genetically engineered models. The primary aim of our study was a comprehensive morphological description of the development of NDP of HD phenotype in the striatum of the rat brain. We compared the progression of NDP in the lesion induced by intrastriatal injection of quinolinic acid (QA) and in rats transgenic for HD. The groups of male rats surviving for 3, 6-7, 14 days, 1, 3, 6, 9 and 12 months after the QA lesion were compared with 2-, 6-, 12-, 18-, 22-24-month-old tgHD rats and age-matched control (intact) counterparts in both groups. The primary morphological feature of the NDP of HD...
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