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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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Impact of NMDA antagonists on neuroplasticity as a biological phenomenon
Kalivodová, Michaela ; Valeš, Karel (advisor) ; Krůšek, Jan (referee)
Neuroplasticity is a fundamental biological phenomenon that accompanies us throughout our lives, both in health and illness. By studying neuroplasticity, we can understand serious neurodegenerative diseases, help remodel the nervous system after damage, or make our actions more efficient in today's world. The first chapter of this thesis will discuss neuroplasticity in the physiological state, describing the development of nervous system, learning and memory, different types of neuroplasticity, and other ways to modify neurogenesis. The following chapter deals with the role of neuroplasticity in disease, its impairment in neuropsychiatric diseases. The most common ones will be described, such as depression, schizophrenia, Alzheimer's disease and Parkinson's disease. The next part of the thesis will discuss the molecular biology of NMDA receptor including structure, activation and excitotoxicity of the NMDA receptor, which is distinct from other receptors. Subsequently, selected NMDA antagonists competitive, non-competitive, uncompetitive, as well as glycine agonists and other selected natural modulators of the NMDA receptor will be described. Finally, this thesis will present the molecular and cellular mechanisms of the BDNF and mTOR pathways, knowledge of which provides a basis for further...
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Calcium homeostasis and modulation of nociceptive synaptic transmission
Sojka, David
This study was designed to improve our knowledge regarding mechanisms of nociceptive signaling at spinal cord level. One of the forms of spinal cord synaptic transmission modulation is central sensitization, a manifestation of synaptic plasticity at spinal cord level, which was found to be present at many chronic pain syndromes. This study deals mainly with a development of calcium imaging technique with a final goal to study mechanisms of central sensitization in vitro on population of dorsal horn neurons. We have analyzed synaptically evoked intracellular Ca changes as a result of dorsal root stimulation in a superficial dorsal horn area in spinal cord slices and found two types of Ca responses: one synchronized with electrical stimulation and a second one, delayed response due to Ca release from internal stores. The delayed Ca release was not previously shown to be present in these neurons and it was not dependent on activation of ionotropic glutamatergic receptors, suggesting involvement of metabotropic receptor pathway. The presence of this delayed type of Ca response could have a significant role in the induction of some types of chronic pain syndromes, since intracellular calcium increase is thought to be a key trigger point in spinal cord neurons sensitization. An important role in neuronal calcium...
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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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The influence of zinc ions on ionotropic glutamate receptors
Fraňková, Denisa ; Krůšek, Jan (advisor) ; Adámek, Pavel (referee)
Zinc is one of the most abundant divalent metal ion in the central nervous system, where it serves as regulator of many proteins (channels, receptors, pump...), product of neurosecretion or cofactor. The highest concentration of zinc in synaptic vesicles of the specific neurons, which are called zinc-containing neurons and it is subset of glutamatergic neurons. The cumulation of zinc in the synaptic neurons is arranged mostly by transporter ZnT3. A concentration of zinc in the synaptic's vesicles is about 1mmol/l and maybe higher. The zinc-containing neurons are mostly in forebrain, where create complex and neuronal network in mammalian's brain, which conect most of cerebral cortex and limbic system (Frederickson et al. 2000). Zinc is released from synapses after a stimulation (Vogt et al. 2000) and then it affects a lot of receptors, for example postsynaptic NMDA receptors (Koh & Choi 1994) and Ca2+ permeable AMPA and cainate receptors (Hong Z. Yin 1995), voltage-gated Ca2+ channels (Atar et al. 1995) and GABAA receptors (Ruiz et al. 2004). This bachelor thesis summarizes the efekt Zn2+ on the ionotropic glutamate receptors. It is mostly adressed on the NMDA receptors, which are the most affected by zinc. The first chapter is about structure of ionotropic glutamate receptors, which is followed up other...
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Calcium homeostasis and modulation of nociceptive synaptic transmission
Sojka, David
This study was designed to improve our knowledge regarding mechanisms of nociceptive signaling at spinal cord level. One of the forms of spinal cord synaptic transmission modulation is central sensitization, a manifestation of synaptic plasticity at spinal cord level, which was found to be present at many chronic pain syndromes. This study deals mainly with a development of calcium imaging technique with a final goal to study mechanisms of central sensitization in vitro on population of dorsal horn neurons. We have analyzed synaptically evoked intracellular Ca changes as a result of dorsal root stimulation in a superficial dorsal horn area in spinal cord slices and found two types of Ca responses: one synchronized with electrical stimulation and a second one, delayed response due to Ca release from internal stores. The delayed Ca release was not previously shown to be present in these neurons and it was not dependent on activation of ionotropic glutamatergic receptors, suggesting involvement of metabotropic receptor pathway. The presence of this delayed type of Ca response could have a significant role in the induction of some types of chronic pain syndromes, since intracellular calcium increase is thought to be a key trigger point in spinal cord neurons sensitization. An important role in neuronal calcium...
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