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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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The effect of the canonical Wnt singalling pathway on the differentiation of polydendrocytes after ischemic brain injury
Knotek, Tomáš ; Anděrová, Miroslava (advisor) ; Romanyuk, Natalyia (referee)
Polydendrocytes, or NG2 glia, are fourth type of glial cells in mammal central nervous system. In the adult brain, NG2 glia represent important cell type with respect to their role in gliogenesis and nervous tissue regeneration following injury. Ligands from the Wingless/Int (Wnt) family play key role in proliferation and differentiation of NG2 glia and they can also influence regeneration of nervous tissue after ischemia. The aim of this thesis was to elucidate the role of NG2 glia in neurogenesis and gliogenesis following ischemic brain injury and investigate the impact of Wnt signalling on the reaction of NG2 glia to this type of injury. To fulfil these aims, transgenic mouse strains with tamoxifen-inducible recombination, that enabled simultaneous expression of red fluorescent dye and either activation or inhibition of the Wnt signalling pathway in NG2 glia, were employed. To induce ischemic injury, middle cerebral artery occlusion model was used. Changes in differentiation and electrophysiological properties of NG2 glia were analysed using patch-clamp technique. Activation of the Wnt signalling pathway under physiological conditions and 7 days after ischemic injury led to increased differentiation of NG2 glia toward astrocytes, while 3 days after ischemic injury activation of this signalling...
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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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The effect of the canonical Wnt singalling pathway on the differentiation of polydendrocytes after ischemic brain injury
Knotek, Tomáš ; Anděrová, Miroslava (advisor) ; Romanyuk, Natalyia (referee)
Polydendrocytes, or NG2 glia, are fourth type of glial cells in mammal central nervous system. In the adult brain, NG2 glia represent important cell type with respect to their role in gliogenesis and nervous tissue regeneration following injury. Ligands from the Wingless/Int (Wnt) family play key role in proliferation and differentiation of NG2 glia and they can also influence regeneration of nervous tissue after ischemia. The aim of this thesis was to elucidate the role of NG2 glia in neurogenesis and gliogenesis following ischemic brain injury and investigate the impact of Wnt signalling on the reaction of NG2 glia to this type of injury. To fulfil these aims, transgenic mouse strains with tamoxifen-inducible recombination, that enabled simultaneous expression of red fluorescent dye and either activation or inhibition of the Wnt signalling pathway in NG2 glia, were employed. To induce ischemic injury, middle cerebral artery occlusion model was used. Changes in differentiation and electrophysiological properties of NG2 glia were analysed using patch-clamp technique. Activation of the Wnt signalling pathway under physiological conditions and 7 days after ischemic injury led to increased differentiation of NG2 glia toward astrocytes, while 3 days after ischemic injury activation of this signalling...
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Membrane properties of NG2 glia in CNS
Knotek, Tomáš ; Anděrová, Miroslava (advisor) ; Hrčka Krausová, Barbora (referee)
NG2 glia represent a new type of glial cells in central nervous system, which does not belong to astrocytes, oligodendrocyte or microglia. and their most frequent marker is chondroitine sulphate proteoglycan NG2. These cells keep their proliferation ability in adult brain and it is generally accepted that they can differentiate into oligodendrocytes. This thesis summarize the current knowledge about membrane properties of NG2 glia, namely expression of numerous types of ion channels and ionotropic and metabotropic receptor on their membrane. NG2 glia express outwardly and inwardly rectifying K+ channels, Ca2+ activated K+ channels and two-pore domain K+ channels. Interestingly, they also express voltage gated Na+ channels, L, T, P/Q and N type Ca2+ channels and voltage gated Cl- channels. Furthermore, nonspecific cationic channels, such as HCN and TRP, were identified in NG2 glia and they express Na+ /Ca2+ exchanger at high level. There are also ionotropic and metabotropic glutamate and GABA receptors on NG2 glia membrane, together with nicotinic and muscarinic receptors, adrenergic and glycine receptors, metabotropic and ionotropic purinergic receptors, receptors for serotonine, dopamine and histamine. Ion channels and receptors in NG2 glia play an important role in their proliferation,...
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Differentiation potential of polydendrocytes in pathological states of central nervous system
Pavlištová, Tereza ; Anděrová, Miroslava (advisor) ; Smejkalová, Terézia (referee)
NG2 cells also called polydendrocytes or oligodendrocyte progenitors comprise fourth type of glial cells in the brain. Ng2 glia express distinct markers on their cell surface, which can be used for their identification. Particularly, NG2 proteoglycan chondroitin sulphate and receptors for platelet-derived growth factor belong to the main markers. Polydendrocytes arise in two canals of spinal cord and also in the ventral part of frontal brain, telencephalon and diencephalon. Population of NG2 cells is heterogeneous because they differ morphologically, by their electrophysiological properties and distinct differentiation potential depending on localization in brain. In conditions in vitro, polydendrocytes can differentiate into oligodendrocytes, protoplasmic astrocytes or neurons. In early postnatal brain, NG2 glia give rise to astrocytes, but most of these cells remain in the mature state or change themselves to oligodendrocytes. Pathological states of the central nervous system cause an activation of polydendrocytes, they start to be hypertrophied and increase expression of NG2 proteoglycan. Reaction of these cells is influenced by environment and chemical factors, for example growth factors, morphogens and cytokines. Depending on the type of CNS disorder the differentiation potential of NG2 glia...
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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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