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Role of glycosylation of ionotropic glutamate receptors in mammalian neurons
Danačíková, Šárka ; Horák, Martin (advisor) ; Kriška, Ján (referee)
Glutamate is the most abundant excitatory neurotransmitter in the mammalian central nervous system. There are two distinct types of glutamate receptors, ionotropic and metabotropic, present in the mammalian excitatory synapses. My thesis is focused on the ionotropic glutamate receptors, which play critical roles in learning and memory formation. The main subtypes of ionotropic glutamate receptors are α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and kainate receptors. All types of the ionotropic glutamate receptors, which are assembled as tetramers, contain many glycosylation sites, which can be modified by glycans or monosaccharides. The glycans and monosaccharides attached to the ionotropic glutamate receptors have been shown to regulate key processes such as folding of the subunits, transport to the cell surface as well as their functional properties. Recent literature also suggests that many neurological and psychiatric disorders such as schizophrenia exhibit abnormal glycosylation of ionotropic glutamate receptors. Thus, understanding of the molecular mechanisms, which regulate the glycosylation of the ionotropic glutamate receptors, may be important for developing new therapies for the patients with altered functioning of the glutamatergic synapses in the...
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Role of glial cells in pathophysiology of demyelinating diseases of the nervous system
Holásek, Michal ; Kriška, Ján (advisor) ; Pivoňková, Helena (referee)
Glial cells, such as oligodendrocytes, Schwann cells, NG2 glia, astrocytes, and microglia, play a major role in the homeostasis of the nervous system, including the myelin sheath maintenance. Enveloping myelin sheaths produced by oligodendrocytes and Schwann cells, provide a mechanical, isolating, and trophic support to the axons. Importantly, a disruption of a certain component or a dysregulation of a specific process may lead to the collapse and the loss of the myelin sheath, known as demyelination. Axonal demyelination is a pathological condition characteristic of different neurological diseases, such as multiple sclerosis, acute disseminated encephalomyelitis, Charcot-Marie- Toth disease, or Lyme neuroborreliosis. Since, demyelinating diseases are still more prevalent in the population, a suitable and effective treatment is crucial for the patients. However, treatment is not available, which results from an insufficient understanding of pathological mechanisms, low permeability through the blood-brain barrier, and a limited regenerative capacity of the nervous system. Therefore, further research in the field of demyelinating diseases is necessary. Key words: oligodendrocyte precursor cell, oligodendrocyte, Schwann cell, myelination, acute disseminated encephalomyelitis, multiple sclerosis,...
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Small extracellular vesicles as microRNA carriers and their role in neural cell regeneration
Šprincl, Vojtěch ; Romanyuk, Natalyia (advisor) ; Kriška, Ján (referee)
Acute spinal cord injury is a serious type of injury, the treatment of which still represents a challenge for contemporary medicine. Neural stem cells (NSCs) transplantation is one of many promising ways to contribute to the regeneration of damaged tissue. NSCs communicate with the rest of the tissue by means of small extracellular vesicles (sEVs), in which their regenerative potential is thus assumed. The aim of this thesis is to verify the antiapoptotic effect of sEVs isolated from the culture medium of two types of NSCs in an rat in vitro model of spinal cord injury. To meet this goal, different methods of isolating sEVs from the culture medium were tested. Subsequently, sEVs were characterized according to their size and the presence of surface markers. This thesis includes an PCR analysis of the cargo of sEVs, which showed an abundance of neuroprotective and antiapoptotic miRNAs. Fluorescent staining of sEVs proved that sEVs penetrate into the cytoplasm of stem cells. Finally, sEVs were applied to a rat in vitro model of spinal cord injury and their neuroprotective effect was demonstrated using the immunoblotting method. Keywords Small extracellular vesicles, exosomes, acute spinal cord injury, regeneration of nervous tissue, miRNA, microRNA, neural stem cells
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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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Behavioral testing of animals after experimental spinal cord injury.
Freislebenová, Hana ; Machová Urdzíková, Lucia (advisor) ; Kriška, Ján (referee)
Spinal cord injury is one of the most serious injury that leads to a decrease in the quality of life both physically and mentally. Although there is currently no effective treatment, great efforts are being made to develop new treatments. The effectiveness of experimental treatment is verified by behavioral tests performed on animal models, where rats are the most suitable ones for this type of injury. Behavioral tests are divided into several groups depending on what the testing is focused on. Locomotor tests examine the function of a locomotive apparatus, motor tests are used to determine the function of skeletal muscles not primarily involved in locomotion, sensory and motor tests test the functionality of sensory and motor apparatus and their interconnection, sensory tests are designed to test responses to sensory stimuli. Electrophysiological tests and functional magnetic resonance imaging are part of a series of special tests that use artificially induced electrical stimuli to measure muscle activity. This thesis is focused on detailed description of selected behavioral tests, their functionality and comparison of their advantages and disadvantages.
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The role of the Wnt signaling pathway in the regeneration following ischemic brain injury
Kriška, Ján ; Anděrová, Miroslava (advisor) ; Stuchlík, Aleš (referee) ; Zíková, Martina (referee)
The role of the Wnt signaling pathway in the regeneration following ischemic brain injury Focal cerebral ischemia results in the loss of neural cells, which may cause permanent disability. At the same time, there are precursor cells (neural stem/progenitor cells and NG2 glia) that naturally reside in the postnatal brain and may proliferate and give rise to other cell types. Their fate is to a large extent influenced by morphogens of the Wnt and Shh family. However, the role of these cellular pathways in differentiation of precursor cells is still enigmatic. For this reason, we employed transgenic mice that enabled us to inhibit or hyper-activate the canonical Wnt signaling pathway, or to map the fate of NG2 cells. The induction of ischemia was achieved by the occlusion of the middle cerebral artery. The changes in the differentiation potential were characterized at the mRNA, protein, and functional levels. First, we evaluated neural stem/progenitor cells isolated from neonatal mice under physiological conditions and found out that Wnt signaling promotes neurogenesis and suppresses gliogenesis. Next, we focused on adult mice and detected a smaller impact of Wnt signaling on their differentiation potential. Nonetheless, its effect was more profound after the induction of ischemia, as we identified...
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Behavioral testing of animals after experimental spinal cord injury.
Freislebenová, Hana ; Machová Urdzíková, Lucia (advisor) ; Kriška, Ján (referee)
Spinal cord injury is one of the most serious injury that leads to a decrease in the quality of life both physically and mentally. Although there is currently no effective treatment, great efforts are being made to develop new treatments. The effectiveness of experimental treatment is verified by behavioral tests performed on animal models, where rats are the most suitable ones for this type of injury. Behavioral tests are divided into several groups depending on what the testing is focused on. Locomotor tests examine the function of a locomotive apparatus, motor tests are used to determine the function of skeletal muscles not primarily involved in locomotion, sensory and motor tests test the functionality of sensory and motor apparatus and their interconnection, sensory tests are designed to test responses to sensory stimuli. Electrophysiological tests and functional magnetic resonance imaging are part of a series of special tests that use artificially induced electrical stimuli to measure muscle activity. This thesis is focused on detailed description of selected behavioral tests, their functionality and comparison of their advantages and disadvantages.
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Role of glycosylation of ionotropic glutamate receptors in mammalian neurons
Danačíková, Šárka ; Horák, Martin (advisor) ; Kriška, Ján (referee)
Glutamate is the most abundant excitatory neurotransmitter in the mammalian central nervous system. There are two distinct types of glutamate receptors, ionotropic and metabotropic, present in the mammalian excitatory synapses. My thesis is focused on the ionotropic glutamate receptors, which play critical roles in learning and memory formation. The main subtypes of ionotropic glutamate receptors are α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and kainate receptors. All types of the ionotropic glutamate receptors, which are assembled as tetramers, contain many glycosylation sites, which can be modified by glycans or monosaccharides. The glycans and monosaccharides attached to the ionotropic glutamate receptors have been shown to regulate key processes such as folding of the subunits, transport to the cell surface as well as their functional properties. Recent literature also suggests that many neurological and psychiatric disorders such as schizophrenia exhibit abnormal glycosylation of ionotropic glutamate receptors. Thus, understanding of the molecular mechanisms, which regulate the glycosylation of the ionotropic glutamate receptors, may be important for developing new therapies for the patients with altered functioning of the glutamatergic synapses in the...
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