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Otimization of a dose of temozolomide for efficient reduction of adult neurogenesis in the laboratory rat
Pištíková, Adéla ; Stuchlík, Aleš (advisor) ; Jiruška, Přemysl (referee)
The goal of this study is to find an optimal dose of cytostatic Temozolomide (TMZ) for Long-Evans strain of rats. This dose should reduce neurogeneis while having a minimal pernicious health side-effects. Temozolomide is newly used to suppress neurogenesis but similarly to any other cytostatic has an effect on all dividing cells in an organism. This can affect health of an animal. Contrary to the mice, there was no systematic attempt to establish optimal dose. In our experiment rats were divided into four groups - one control group and three treatment groups which received different doses of temozolomide (10, 25, 40 mg/kg of TMZ). To detect level of neurogenesis cells were labeled by bromodeoxyuridine. During the experiment blood element counts were assessed, sensorimotoric tests were conducted, and weight increment was monitored. The results indicate that dose of 10mg/kg is adequate as it reduces neurogenesis by 64% compared to the control group and does not significantly differ from higher doses. In this group weight increment is comparable with the control group, while in the higher doses of TMZ weight increment is significantly lower. Effect of myelosupression is same for all treatment groups.
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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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Adult neurogenesis in the hippocampus and spatial navigation
Dostálová, Magdalena ; Stuchlík, Aleš (advisor) ; Jiruška, Přemysl (referee)
Hundreds to thousands of new granule neurons are born every day in the hippocampus within the whole life. Inspite of intensive research of the last decades, their function remains unclear. Their participation in spatial memory and the ability of orientation is assumed. Results from behavioral tests like the Morris water maze, the radial maze and many other testing tasks, are often contradictory. Nevertheless, it is highly probable that neurogenesis plays a role in pattern separation and long-term relational memory. Further studies and especially reliable methods of ablation and detection are required for deeper insight into this issue.
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Differentiation potential of polydendrocytes after focal cerebral ischemia
Filipová, Marcela ; Anděrová, Miroslava (advisor) ; Jendelová, Pavla (referee)
Ischemic injury leeds to sequence of pathophysiological events, which are accompanied by a release of growth factors and morphogens that significantly affect cell proliferation, migration and also their differentiation. Following ischemia, besides enhanced neurogenesis and gliogenesis in subventricular zone of the lateral ventricles and gyrus dentatus of the hippocampus, neurogenesis/gliogenesis also occurs in non-neurogenic regions, such as cortex or striatum. Recently, the attention was turned to a new glial cell type, termed polydendrocytes or NG2 glia. Under physiological conditions, these cells are able to divide and differentiate into mature oligodendrocytes due to they have often been equated with oligodendrocyte precursor cells. Based on recent reports, polydendrocytes are also able to generate protoplasmic astrocytes (Zhu et al., 2008) and neurons in vitro (Belachew et al., 2003), however their ability to differentiate into astrocytes or neurons under physiological or pathological conditions is still highly debated. Therefore, we have investigated the effect of different growth factors and morphogens, specifically brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and a morphogen sonic hedgehog (Shh), on...
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Neurogenesis in the adult brain, its regulation and possible functions
Pištíková, Adéla ; Stuchlík, Aleš (advisor) ; Jiruška, Přemysl (referee)
In this thesis I examine neurogenesis in the adult brain. Neurogenesis takes place in two main neurogenic areas. One area is located at the side of the forebrain ventricle and the other in dentate gyrus of the hippocampus. The forebrain ventricle neurogenesis is important for olfactory discrimination and olfactory memory. In the hippocampus, its function is unclear, but there are several hypotheses about its possible significance. We assume it might function in pattern separation and also be involvedin preventing interference between memory traces. The last chapter I dedicate to the positive and negative regulation of neurogenesis. The manipulations enhancing neurogenesis include voluntary physical activity, enriched environment and SSRI antidepressants. The negative impact on neurogenesis is exerted among other factors by stress, irradiation and a cytostatic Temodal, which is used methodologiclly to block neurogenesis.
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Induction of neurogenesis and gliogenesis after ischemic injury of CNS
Filipová, Marcela ; Moravec, Jan (referee) ; Anděrová, Miroslava (advisor)
Ischemic injury (stroke) is one of the most common causes of death and disability in humans. Discovery of adult neurogenesis and possibilities to induce neurogenesis by cytokines brought new approaches and hopes in treating the ischemic lesion in future. The aim of this thesis is to describe cellular and molecular mechanisms of neurogenesis, mainly those discovered within last ten years. The first part describes generation of new neurons in the brain under physiological conditions, which is localized in the dentate gyrus of the hippocampus and in the subventricular zone of the lateral ventricles (i.e. in principal neurogenic regions). The second part describes animal models used for studying ischemic injury in rodents and moreover, it focuses on patophysiology of ischemic brain injury, which is accompanied by astrocyte and microglia activation. Further, the ischemia-induced neurogenesis is described in these two major neurogenic regions. Also the important role of NG2 glial cells in central nervous system (CNS) regeneration is pointed out. According to recent findings NG2 glia that are present in all regions of CNS might serve as a potential source of cells for directed differentiation into oligodendrocytes, astrocytes and even neurons during CNS repair/regeneration. In the last part of this work,...
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Quest for protein biomarkers of neural stem cells differentiation
Skalníková, Helena ; Halada, Petr ; Vodička, Petr ; Motlík, Jan ; Horing, O. ; Jensen, O. N. ; Gadher, S. J. ; Pelech, S. ; Kovářová, Hana
Understanding neurogenesis and neural cell differentiation presents a unique challenge for treatment of nervous system disorders. To gain more insight about molecular mechanism of differentiation of neural cells, we applied different proteomic approaches using classical 2-DE followed by MS and antibody microarrays. Based on 2-DE, profile of constituent proteins of neural stem cells and their differentiated progenies was estabilished at first and then the protein species that are significantly up or down regulated during the differentiation were selected. Differentiation of neural cells was accompanied by changes in the expression of proteins involved in DNA and RNA binding, mRNA processing and transport, stress responses, iron storage and redox regulation. Immunoblot verified changes of hnRNP A1, hnRNP A2/B1, RafB, heme-oxygenasy 2, GRK2 proteins and alphaB-crystallin (S45), CDK1/2 (Y15), PKC mu (S738+S742), proline-rich Akt substrate (T246) phosphorylations during differentiation.
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