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Vliv paralytického jedu lumčíka, \kur{Habrobracon hebetor}, na svalovou tkáň zavíječe, \kur{Ephestia kuehniella} a octomilky, \kur{Drosophila melanogaster}
PODLAHOVÁ, Šárka
The ectoparasitoid wasp Habrobracon hebetor uses its effective venom for inducing neuromuscular paralysis to ensure the proper development of its progeny in the host attacked. However, the associated mechanism of the paralysis is not known yet. The action of the venom was studied in the muscle tissue of its host larvae Ephestia kuehniella and in the model organism Drosophila melanogaster using transmission electron microscopy (TEM). Preparation of the samples for TEM was optimized to protect tissue integrity and to minimalize artefacts. The results revealed that the wasp venom affected neither the organization of muscle fibres nor the structure of mitochondria. Furthermore, potential D. melanogaster mutants of glutamate receptor subunits GluRIIA and GluRIIB were analyzed, and the role of glutamate receptors in regulation of paralysis was discussed.
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Neurosteroid modulation of ligand-gated ion-channel activity
Krausová, Barbora ; Vyklický, Ladislav (advisor) ; Moravec, Jan (referee)
The term neurosteroids refers to steroids that are synthetized in the nervous tissue from cholesterol or steroidal precursors from peripheral sources. These compounds affect the neuronal excitability by modulating the function of some ligand-gated ion channels. NMDA (N methyl D aspartate) receptors are glutamate gated ion channels involved in excitatory synaptic transmission, synaptic plasticity and excitotoxicity. GABAA ( aminobutyric acid type A) receptors mediate most of the inhibitory synaptic transmission in the mammalian brain and are targeted by many clinically important drugs. Function of NMDA and GABAA receptors can by affected by neurosteroids, both positively and negatively. The aim of this work is to summarize the current knowledge about the neurosteroid effects on the function of GABAA a NMDA receptors and suggest the physiological role and the potential therapeutic use of the neurosteroids as a regulator of some functions of the central nervous system.
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Expression of AMPA glutamate receptor subunits in the suprachiasmatic nucleus of the rat
Červená, Kateřina ; Bendová, Zdeňka (advisor) ; Zemková, Hana (referee)
The main mammalian circadian pacemaker stored in suprachiasmatic nuclei of the hypothalamus (SCN) is adapted to changes in the external environement by synchronization of its endogenous period with periodic changes of light and dark during day and night. The information about light travels via glutamatergic retinohypothalamic tract to the ventrolateral part of the SCN. Activation of ionotropic glutamate receptors in this area provably mediates the transfer of information about light on the transcriptional mechanism of light-sensitive cells. The role of the NMDA type of ionotropic glutamate receptors is well studied in this field and it is known that some NMDA receptor subunits show a circadian rhythm and an increased expression after a light pulse. Signalization via AMPA type receptors is much less elucidated. The aim of this thesis was to determine which AMPA receptor subunits are expressed in the SCN of the rat and if these subunits show a daily rhythm of expression and a reactivity to light pulse, as well as to outline the possible roles of distinct AMPA receptor subunits in the SCN. Keywords: circadian rhythms, suprachiasmatic nuclei, glutamate receptors, AMPA
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Calcium signaling of oligodendroglial lineage cells in the animal model of schizophrenia
Kročianová, Daniela ; Anděrová, Miroslava (advisor) ; Stuchlík, Aleš (referee)
Schizophrenia is a neurological disorder with a complex psychopathology, which is far from fully elucidated. In the patients with this disorder, changes on anatomical, cellular, and neurotransmitter level have been found. The aim of this work is to elucidate the function of specific ionotropic glutamate receptors in NG2 glia in the hippocampus of a mouse model of schizophrenia. For this purpose, a mouse model of schizophrenia was generated and validated using immunohistochemistry and behavioural testing. Mice with NG2 glia labelled by a fluorescent protein with a calcium indicator also in NG2 glia were used to observe the activity of glutamate channels and the properties of the extracellular space in these mice. Changes were found in the schizophrenic animals when compared to control animals in the numbers of hippocampal oligodendrocyte lineage cells, in prepulse inhibition and in both volume fraction and tortuosity of the extracellular space in hippocampus. Moreover, the percentage of cells responding to glutamate receptor agonists in NG2 glia in hippocampus also differed significantly between the schizophrenic and the control animals. In conclusion, it can be said that we were able to observe significant changes in the mouse model of schizophrenia that we generated in comparison to control...
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Zebrafish as a model to study the glutamate receptor mediated excitatory neurotrasmission
Chumchal, Lukáš ; Balík, Aleš (advisor) ; Pangrácová, Marie (referee)
Glutamate is the most prominent excitatory neurotransmitter in the vertebrate brain and is used by most synaptic connections in the cortex. Signal transduction on these neurons is mediated by ionotropic glutamate receptors, including the NMDA receptor family. With the development of molecular biological methods and the advent of genomics, genetic changes found in ionotropic glutamate receptors were tested, as well as substances that modulate their activity. Since a large number of genetic changes found, rodents have ceased to be a sufficiently robust system for some, for example, behavioural studies. In these types of studies, the model organism Danio rerio could replace rodents. The use of this model organism could thus expand knowledge about the evolution and physiology of glutamate receptors. This work aims to summarize the current knowledge about the use of Dania rerio in the research of glutamate receptors, especially NMDA type in the central nervous system. This work also focuses on the description of specific behavioural tests available for the analysis of these receptors.
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Intracellular domain of glutamate ion channels and its role in the emergence of pathophysiological states
Sadílková, Lucie ; Balík, Aleš (advisor) ; Kolář, David (referee)
Glutamate mediates most of the excitatory neurotransmissions in the central nervous system of mammals. Its effect depends on the presence of glutamate receptors on postsynaptic neurons. NMDA receptors are class of the ionotropic glutamate receptors and are necessary for normal brain function such as synaptic plasticity, learning, memory and correct development of neu- rons. NMDA receptors are also involved in the pathophysiology of many neurodevelopmental and neuropsychiatric diseases. The aim of this work is to evaluate the current knowledge of the role of the intracellular part of NMDA receptors for their function, particularly with respect to the regulation of their localization at excitatory synapses. In addition, it also provides an over- view of the genetic changes found in this part of the receptor, their effect on the functional properties of the receptor and then also a possible link to specific disease.
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Structural and pharmacological determinants of NMDA receptor channel gating
Ladislav, Marek ; Krůšek, Jan (advisor) ; Bendová, Zdeňka (referee) ; Zemková, Hana (referee)
N-methyl-D-aspartate receptors (NMDARs) are heterotetramers containing two obligatory glycine-binding (GluN1) and two glutamate/glycine-binding (GluN2/3) subunits. These receptors mediate excitatory synaptic transmission in the central nervous system and play a key role in high order neuronal processes as a learning and formation of memory. It has been shown that dysregulation of NMDARs is involved in the pathophysiology of neurological and psychiatric disorders. Each receptor is composed of four protomers exhibiting a conserved domain organization. The most distal part to the cell membrane is the amino-terminal domain that is linked to the ligand binding domain (LBD), which is connected to the pore-forming transmembrane domain (TMD) communicating with the intracellular carboxy-terminal domain. LBD and TMD are connected via three polypeptide chains - linkers. Channel opening is the key step in the NMDAR gating that allows the flux of ions across the membrane. The energy of agonist binding-evoked conformational changes is transferred via linkers to M3 helices forming an ion channel. The rearrangement of M3 helices in activated receptor makes the central cavity of the channel accessible. The details of energy transfer are not yet fully characterized, although accurate knowledge of the receptor gating...
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Glutamate receptors in NG2-glial cells: gene profiling and functional changes after ischemic brain injury
Waloschková, Eliška ; Anděrová, Miroslava (advisor) ; Růžička, Jiří (referee)
Glutamate is the main excitatory neurotransmitter in the mammalian brain and its transmission is responsible for higher brain functions, such as learning, memory and cognition. Glutamate action is mediated by a variety of glutamate receptors, though their properties were until now studied predominantly in neurons. Glutamate receptors are expressed also in NG2-glia, however their role under physiological conditions as well as in pathological states of the central nervous system is not fully understood. The aim of this work is to elucidate the presence, composition and function of these receptors in NG2-glia under physiological conditions and following focal cerebral ischemia. For this purpose we used transgenic mice, in which NG2-glia are labeled by a fluorescent protein for their precise identification. To analyze the expression pattern of glutamate receptors in NG2-glia we employed single-cell RT-qPCR. Furthermore, we used calcium imaging to characterize their functional properties.
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Expression of AMPA glutamate receptor subunits in the suprachiasmatic nucleus of the rat
Červená, Kateřina ; Bendová, Zdeňka (advisor) ; Zemková, Hana (referee)
The main mammalian circadian pacemaker stored in suprachiasmatic nuclei of the hypothalamus (SCN) is adapted to changes in the external environement by synchronization of its endogenous period with periodic changes of light and dark during day and night. The information about light travels via glutamatergic retinohypothalamic tract to the ventrolateral part of the SCN. Activation of ionotropic glutamate receptors in this area provably mediates the transfer of information about light on the transcriptional mechanism of light-sensitive cells. The role of the NMDA type of ionotropic glutamate receptors is well studied in this field and it is known that some NMDA receptor subunits show a circadian rhythm and an increased expression after a light pulse. Signalization via AMPA type receptors is much less elucidated. The aim of this thesis was to determine which AMPA receptor subunits are expressed in the SCN of the rat and if these subunits show a daily rhythm of expression and a reactivity to light pulse, as well as to outline the possible roles of distinct AMPA receptor subunits in the SCN. Keywords: circadian rhythms, suprachiasmatic nuclei, glutamate receptors, AMPA
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Neurosteroid modulation of ligand-gated ion-channel activity
Krausová, Barbora ; Vyklický, Ladislav (advisor) ; Moravec, Jan (referee)
The term neurosteroids refers to steroids that are synthetized in the nervous tissue from cholesterol or steroidal precursors from peripheral sources. These compounds affect the neuronal excitability by modulating the function of some ligand-gated ion channels. NMDA (N methyl D aspartate) receptors are glutamate gated ion channels involved in excitatory synaptic transmission, synaptic plasticity and excitotoxicity. GABAA ( aminobutyric acid type A) receptors mediate most of the inhibitory synaptic transmission in the mammalian brain and are targeted by many clinically important drugs. Function of NMDA and GABAA receptors can by affected by neurosteroids, both positively and negatively. The aim of this work is to summarize the current knowledge about the neurosteroid effects on the function of GABAA a NMDA receptors and suggest the physiological role and the potential therapeutic use of the neurosteroids as a regulator of some functions of the central nervous system.
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