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Glial cells in central nervous system pathology: the role of Wnt signaling
Bronišová, Denisa ; Kriška, Ján (advisor) ; Heleš, Mário (referee)
Wnt signaling plays an important role in regulating cell growth, differentiation, or movement. This represents a potential in the treatment of pathologies in which the proliferation or differentiation of new cells could be key to the regeneration and mitigation of the consequences of the disease. Glial cells are more than just a glue for neurons, and they have important roles in pathologies in maintaining cell metabolism and survival, and brain functioning in general. The aim of this bachelor thesis is to provide a literature review of the roles of Wnt signaling in glial cells in the healthy brain, but especially in central nervous system (CNS) pathologies. The work provides an overview of the main types of glial cells in the CNS, a description of three Wnt signaling pathways, and focuses in detail on selected CNS pathologies and the role and changes of Wnt signaling that occur in these pathologies. Further research utilizing the potential of Wnt signaling in glial cells might lead to the development of novel therapies that could change the fate of patients with CNS diseases.
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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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Incidence and role of the purinergic P2X7 receptor in the immune system
Piskačová, Kateřina ; Zemková, Hana (advisor) ; Červená, Kateřina (referee)
It has been shown recently that extracellular ATP and its metabolite adenosine are key mediators in the immune system. Depending on the concentration, ATP may act as an activator or an inhibitor to the immune response, whereas adenosine is generally well known as a specific immunosupressor. Signals delivered by extracellular ATP and adenosine are detected and transduced by purinergic P2- and P1- receptors, respectively. In principle, all cells of the immune system express P2X, P2Y and adenosine P1 receptors on their plasmatic membrane. Therefore, the purinergic signaling extends to all components of the immune and inflammatory responses, including neurodegenerative diseases. This knowledge triggered a wave of interest in research, development and synthesis of new compounds having effect on P1- and P2- receptors that could help in the treatment of chronic inflammatory diseases and neurodegenerative diseases. This bachelor thesis will summarize the most recent knowledge on the role of the P2X7 receptor in these processes. This subtype of P2-receptor is unique because it is involved in the release of cytokines from immune cells and plays a role in the cell growth and apoptosis.
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Opioids and neuroprotection: the role of glial cells
Honc, Ondřej ; Novotný, Jiří (advisor) ; Kováčová, Ľubica (referee)
High energy deamand and insulation via the blood-bain barrier are the main reasons for neuronal sensitivity to oxygen or energy deficiency. Even short or mild periods of hypoxia/ischemia (H/I) could fataly impact the CNS enviroment. The area on the edge of the tissue affected by H/I and adjacent unaffected tissue is called the penumbra. Here, we can observe additional H/I related processes - gliosis allied with sterile inflammation and censecutive apoptosis. Opioid receptors attenuate H/I impact on CNS in both acute and consecutive phases. In acute phases, opioid receptors regulate ion homeostasis and attenuate glutamate toxicity; in consecutive phases, lower gliosis manifestation. Both these actions have significant neuroprotective effects. Ability of opioid receptor to lower sterile inflammation in CNS could be used in a series of neurodegenerative diseases, eg. Alzheimer disease or amyotrophic lateral screlosis. Glial cells participate on ion homeostasis, glutamate uptake, and production of antiinflammatory substances; one can, therefore, assume that a significant part of neuroprotective effects of OR is related to glial cells. The opioid system and its signaling pathways has not been fully elucidated yet. I present global overview of this phenomenon and describe some recent findings regarding...
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Glial cells and their role in amyotrophic lateral sclerosis
Vaňátko, Ondřej ; Anděrová, Miroslava (advisor) ; Černý, Jan (referee)
Amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) is a progressive neurodegenerative disorder. It affects upper and lower motor neurons in the brain motor cortex, the brain stem and the spinal cord, causing their death, which results in denervation of voluntary muscles. Progressive muscle weakness and atrophy throughout the entire body gradually leads to worsening of the ability to move, speak, chew, swallow and eventually breath. Ultimately it results in affected individual's death due to respiratory muscle failure. Although first identified in 1869, no cure for ALS has been yet found. While early studies focused mainly on the research of motor neurons themselves, the attention has shifted towards glial cells in the past two decades. Glial cells are essential for proper neuron functioning and survival and it appears that they play a major role in ALS progression. The goal of this thesis is to review and summarize findings on the role of glial cells in ALS over the last years, focusing on four specific types of glial cells, namely astrocytes, microglia, oligodendrocytes and NG2-glia. Key words: amyotrophic lateral sclerosis, ALS, motor neuron, glia, astrocyte, microglia, oligodendrocyte, NG2-glia
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Microglia control adenosine A2A-receptor mediated astrogliosis
Svobodová, Magdaléna ; Mladěnka, Přemysl (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Magdaléna Svobodová Supervisor: Assoc. Prof. Přemysl Mladěnka, Ph.D. Assoc. Prof. Maria da Glória Correia da Silva Queiroz, Ph.D. Title of diploma thesis: Microglia control adenosine A2A-receptor mediated astrogliosis In the central nervous system, astrocytes and microglia are the main cells coordinating the inflammatory response. During inflammation, dying or temporarily damaged cells release ATP, as a danger-associated signal molecule, that contributes to the induction of astrogliosis and promotes clearance of the debris by immune cells such as microglia. Adenosine that results from ATP metabolism also stimulates astrogliosis. However, the effects of adenosine on astrogliosis may be more complex, since it also modulates microglia phenotype and microglia have been shown to prevent excessive astroglial proliferation mediated by nucleotides. In this context, ATP and adenosine are assumed as relevant signalling molecules in the control of astrogliosis and its modulation by microglia. However, it is still unknown whether and how microglia modulate adenosine-mediated astrogliosis. The present study aims to clarify the impact of microglia in the control of adenosine-induced astrogliosis. Two...
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Microglia control adenosine A2A-receptor mediated astrogliosis
Svobodová, Magdaléna ; Mladěnka, Přemysl (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Magdaléna Svobodová Supervisor: Assoc. Prof. Přemysl Mladěnka, Ph.D. Assoc. Prof. Maria da Glória Correia da Silva Queiroz, Ph.D. Title of diploma thesis: Microglia control adenosine A2A-receptor mediated astrogliosis In the central nervous system, astrocytes and microglia are the main cells coordinating the inflammatory response. During inflammation, dying or temporarily damaged cells release ATP, as a danger-associated signal molecule, that contributes to the induction of astrogliosis and promotes clearance of the debris by immune cells such as microglia. Adenosine that results from ATP metabolism also stimulates astrogliosis. However, the effects of adenosine on astrogliosis may be more complex, since it also modulates microglia phenotype and microglia have been shown to prevent excessive astroglial proliferation mediated by nucleotides. In this context, ATP and adenosine are assumed as relevant signalling molecules in the control of astrogliosis and its modulation by microglia. However, it is still unknown whether and how microglia modulate adenosine-mediated astrogliosis. The present study aims to clarify the impact of microglia in the control of adenosine-induced astrogliosis. Two...
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Opioids and neuroprotection: the role of glial cells
Honc, Ondřej ; Novotný, Jiří (advisor) ; Kováčová, Ľubica (referee)
High energy deamand and insulation via the blood-bain barrier are the main reasons for neuronal sensitivity to oxygen or energy deficiency. Even short or mild periods of hypoxia/ischemia (H/I) could fataly impact the CNS enviroment. The area on the edge of the tissue affected by H/I and adjacent unaffected tissue is called the penumbra. Here, we can observe additional H/I related processes - gliosis allied with sterile inflammation and censecutive apoptosis. Opioid receptors attenuate H/I impact on CNS in both acute and consecutive phases. In acute phases, opioid receptors regulate ion homeostasis and attenuate glutamate toxicity; in consecutive phases, lower gliosis manifestation. Both these actions have significant neuroprotective effects. Ability of opioid receptor to lower sterile inflammation in CNS could be used in a series of neurodegenerative diseases, eg. Alzheimer disease or amyotrophic lateral screlosis. Glial cells participate on ion homeostasis, glutamate uptake, and production of antiinflammatory substances; one can, therefore, assume that a significant part of neuroprotective effects of OR is related to glial cells. The opioid system and its signaling pathways has not been fully elucidated yet. I present global overview of this phenomenon and describe some recent findings regarding...
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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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The role of glia in neuroprotection
Fider, Jan ; Novotný, Jiří (advisor) ; Telenský, Petr (referee)
Verterbate brain is extremely demanding on energy and oxygen consumption. A few seconds of the oxygen deprivation can disrupt brain homeostasis and cause an ionic imbalance, resulting in neuronal death by apoptosis or necrosis. The mechanisms, that are responsible for protection of the CNS against the disruption of homeostasis are called neuroprotection. Neuroprotection in the brain is mostly provided by glial cells. There are several types of glia in the human brain, but not all of them are responsible for neuroprotection equally. However, in general we can say that all the glial cells are responsible for the maintainance of ionic balance, which play an important role in neuroprotection. Astroglia and mikroglia dominantly contribute to protectiion of the CNS. These cells can be activated by any disruption of the CNS and actively execute a number of neuroprotective actions. Activated astrocytes form astrogliosis, which covers and separates the affected area of the brain from healthy tissue, thereby preventing further spread of ischemic damage. Activated microglia can transform into phagocytes which clean the extracellular space from dead cells and their parts. Neuroprotection research is nowadays very popular. This is because of urgent need better understanding of the causes of neurodegenerative...
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