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The role of glial cells after ischemic stroke and their therapeutic potential.
Gorgol, Anastasija ; Kriška, Ján (advisor) ; Danačíková, Šárka (referee)
Stroke is one of the most common causes of death and disability worldwide. It causes a disruption in the blood flow in the brain. It affects neurons, but also glial cells, which play important roles in the course of the disease. The aim of this bachelor thesis is to provide an overview of the possible therapeutic use of glial cells in ischemic stroke (focal cerebral ischemia). The work also provides an overview of the main types of glial cells in the central nervous system, describes the function of individual glia in the healthy brain and during ischemia, and focuses on their potential in neuroprotection and brain regeneration.
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The effect of stress on astrocytes and their function during brain development in adolescence
Veverka, Jakub ; Nekovářová, Tereza (advisor) ; Telenský, Petr (referee)
Astrocytes have perhaps been historically underestimated in their number of roles regarding brain homeostasis. Recent studies are identifying the pivotal role they play in brain restructuring and how possible disruption of their function could be a predisposing factor for numerous psychiatric diseases. Proper astrocytic function might be of increased significance in adolescence, when major heterochronic brain restructuring occurs, and external stressors are of magnified effect. Regarding the role of astrocytes in synaptic formation/degradation and synaptic cleft substance clearance, the dysfunction of their homeostatic pathways during such a crucial period may predispose the effected person to specific patterns of CNS development. This could prove to be important during the development or progression of psychiatric and psychological disorders. This work will focus on the role of astrocytes during pathologically stressful conditions, the alteration of their function and the researched causes for such events namely during the unique time period of adolescence. It will also comment on the possible effect of such events during adolescence on the appearance or progression of potential psychiatric or psychological disorders later in life. Key words: Astrocytes, stress, brain, adolescence, development
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The effect of methamphetamine on the neuroimmune system
Petrášová, Blanka ; Hejnová, Lucie (advisor) ; Lapka, Marek (referee)
Metamphetamine is worldwide problem and in the Czech republic is 2-3 % of people older than 15 years exposed to it. There are 34,7 thousand long-term users in Czech republic and 19 methamphetamine-related deaths in 2022. The impact on the neuroimmune system has only started to be studied in recent years. Understanding its effect on the neuroimmune system may outline new treatment options, as there is no cure for methamphetamine addiction to date. This paper summarizes its effects on the different components of the neuroimmune system and outlines some substances that could be used in treatment. Key words: methamphetamine, neuroimmune system, inflammation, microglia, astrocytes
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Circadian system as a modulator of neuroinflammation
Kotková, Eliška ; Spišská, Veronika (advisor) ; Dočkal, Tereza (referee)
The circadian system is involved in the regulation of biological rhythms in physiological, behavioural and immune processes. These rhythms can be found in the central nervous system, including the blood-brain barrier, astrocytes, microglia, and the pineal gland, which produces the hormone melatonin. Neuroinflammation is a complex response of the central nervous system to inflammatory stimuli by rhythmic expression of pro-inflammatory and anti-inflammatory mediators or by rhythmic regulation of immune system cells. Studies have examined the influence of genes and proteins of the circadian system, suprachiasmatic nuclei, melatonin, and glial cell rhythms on neuroinflammation. Lipopolysaccharide was used to induce neuroinflammation in these studies. Based on these studies, the effect of melatonin on mikroglia and endothelial cells, and the responses of suprachiasmatic nuclei was evaluted as the most important circadian modulator of neuroinflammation. This thesis describes the basic principles of the circadian system and neuroinflammation, with the last section presenting the modulation of neuroinflammation by the circadian system. Keywords: astrocytes, blood-brain barrier, circadian system, cytokines, immune system, melatonin, microglia, neuroinflammation, suprachiasmatic nuclei
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The role of microglia and astrocytes in Alzheimer's disease
Pospíšilová, Eva ; Telenský, Petr (advisor) ; Svoboda, Jan (referee)
Alzheimer's disease is a neurodegenerative disease that affects the central nervous system and is characterized mainly by problems with memory abilities. With the more aging population, the number of patients with this disease is gradually increasing, so Alzheimer's disease research is becoming one of the main priorities of today's health care. Although the research has been going on for more than a century, the exact causes of the Alzheimer's disease are still unclear. For a long time, the main role was attributed to the pathology of amyloid β and tau protein, the basic pathophysiological features of this disease, but in recent years, it has become clear that microglia and astrocytes also play an important role. These glial cells affect the amount of amyloid β and the hyperphosphorylated tau protein, but they are also crucial for maintaining homeostasis of the central nervous system. Activation of microglia and astrocytes in Alzheimer's disease can lead to disruption of the physiological functions of these neuroglia, and thus to problems with the removal of amyloid and tau protein, but also to the induction of chronic neuroinflammation. This work aims to summarize and organize the basic knowledge about the role of microglia and astrocytes in Alzheimer's disease, while focusing mainly on their role...
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NG2-glia proliferation and differentiation following CNS injuries
Kirdajová, Denisa ; Anděrová, Miroslava (advisor) ; Procházka, Jan (referee) ; Novák, Ondřej (referee)
NG2-glia proliferation and differentiation following CNS injuries Abstract NG2 glia display wide proliferation and differentiation potential under physiological and pathological conditions. They are very well known as precursors of oligodendrocytes, however, following central nervous system (CNS) injury they play an important role in regeneration. For this reason, we examined these features following different types of brain disorders such as focal cerebral ischemia (FCI), cortical stab wound (SW), and demyelination (DEMY) in young (3-months-old) mice, in which NG2 glia are labeled by tdTomato under the Cspg4 promoter. In the case of FCI, the factor of age was also studied using 18-months-old mice. To address these issues, we employed many techniques on tissue/cellular levels, such as single-cell RT- qPCR, single-cell/bulk RNA-sequencing, immunohistochemistry, and the patch-clamp technique in situ. First, such approach enabled us to distinguish two main populations (NG2 glia, oligodendrocytes), each of them comprising four distinct subpopulations. Next, the expression profiling revealed that a subpopulation of NG2 glia expressing GFAP, a marker of reactive astrocytes, appears transiently after FCI. However, following less severe injury, namely the cortical SW and DEMY, subpopulations mirroring different...
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The role of aquaporins in the Alzheimer's disease
Kubísková, Monika ; Turečková, Jana (advisor) ; Vlachová, Viktorie (referee)
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with complex pathophysiology affecting the central nervous system (CNS). In progress of the disease, various pathological changes occur in the brain, leading to neurodegeneration and subsequent impairment of physiological and cognitive functions. Although it is the most common cause of dementia in elderly, currently, there is no effective treatment for AD that that targets its underlying mechanisms. There are different theories as to which process is the key trigger for the development of AD. The generally accepted theory considers increased production of amyloid β (Aβ), its accumulation in the ECS and the formation of amyloid plaques as the main cause of the disease. However, recent studies show that the primary cause of amyloid plaque formation is not increased Aβ production, but rather its impaired clearance through the glymphatic system, the main component of which are aquaporin water channels, specifically aquaporin-4 (AQP4). The goal of this thesis is to provide an overview of the available knowledge on the involvement of aquaporins in AD pathophysiology, with a particular focus on AQP4 and its role in the glymphatic system. Key words: Alzheimer's disease, neurodegeneration, central nervous system, astrocytes, aquaporins,...
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Vlastnosti a regulace objemově-závislých aniontových kanálů u astrocytů.
Harantová, Lenka ; Anděrová, Miroslava (advisor) ; Moravec, Jan (referee)
Animal cells need to preserve constant volume in the face of osmolarity perturbations to function properly. To regain their original volume after hyposmotically induced swelling, most cell types extrude intracellular electrolytes and organic osmolytes accompanied by osmotically driven water. This process is termed regulatory volume decrease and is ensured by various ion channels and transporters. Recently, much attention has been focused on the ubiquitous volume-regulated anion channels activated by cell swelling. VRACs are moderately outwardly rectifying with intermediary conductance, permeable to inorganic anions and organic osmolytes and sensitive to broad-spectrum anion channels blockers. Functional properties of VRACs in astrocytes are particularly interesting, because many brain pathologies, such as ischemia, traumatic brain injury or hyponatremia, are associated with marked astrocytic swelling and VRACs could thus constitute a possible target for therapy of cerebral edema. Furthermore, VRACs are thought to play a role in cell cycle progression, cell migration, apoptosis and intercellular communication. Despite intensive research, VRACs molecular identity and mechanism of their activation and regulation are still unclear. This work summarizes known facts about VRACs, accentuating their...
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Astrocyte volume changes during brain ischemic injury
Mikešová, Michaela ; Anděrová, Miroslava (advisor) ; Zemková, Hana (referee)
Brain ischemic injury is a complex of pathophysiological events following transient or permanent reduction of brain blood flow. It results in a disruption of neuronal and astrocytic physiological functions, long-term reduction of brain blood flow leads to the cell death. Number of recent studies is focused on astrocytes, which might play key roles in surviving cells, including neurons, during ischemic injury. Astrocytes provide many important functions, such as maintenance of ionic homeostasis, prevention of excitotoxicity, scavenging free radicals and others and thus astrocytes may dramatically swell during ischemic conditions and contribute notably to the development of cytotoxic edema. This thesis summarizes mechanisms possibly contributing to the astrocytic swelling during brain ischemic injury as well as methods used for studying astrocyte volume changes and their quantification. Since the brain edema dramatically complicates both course and treatment of ischemic injury, knowledge of mechanisms leading to astrocytic swelling and their volume regulation during ischemia/reperfusion might be used for developing new therapeutic approaches for the treatment of cerebral ischemia, mainly for reduction of negative impact of edema.
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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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