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The effect of structural changes in perineuronal nets and deep cooling on synaptic plasticity and memory of tauopathy mice
Šafránková, Kristýna ; Růžička, Jiří (advisor) ; Telenský, Petr (referee)
Tauopathy is accompanied by both loss of neurons and synapses. The neuronal loss is irreversible with very low chance of functional replacement therapy. However, lost synapses could be restored with proper stimuli. Perineuronal nets (PNNs) are serving as a protecting barrier for neurons, on the other hand they are significantly decreasing the synaptic plasticity. Temporary disintegration of the PNNs by enzymatic therapy might lead to rewiring and accelerate processes of memory and learning. Model of Cold Induced plasticity leads to the withdrawal of significant number of synapses across the brain. The recovery of these could be followed in healthy and diseased animals. Moreover, it can stimulate Cold shock protein dependent neuroprotective mechanisms. This master thesis is focused on these two forms of synaptic plasticity models; forced remodeling of PNNs and model of cold induced synaptic plasticity. Both will serve as a tool to modulate processes of memory and learning in the P301S tauopathy, in mice. In detail, the work will follow changes in the number of synapses at the region of CA1 of hippocampus and synaptic protein levels at level of whole hippocampus and behavioral recovery of pre-trained long-term memory task dependent on dorsal hippocampus. Key words: Perineuronal nets, aggrecan,...
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Na/K-ATPase in spleen lymphocytes and hippocampus of rat; effect of morphine, stimulation by mitogen and effect of stress induced by deprivation from sleep
Kaufman, Jonáš ; Svoboda, Petr (advisor) ; Hejnová, Lucie (referee)
This work was oriented to studies of sodium and potassium dependent adenosinetriphosphatase, Na+ /K+ ATPase, which is selectively inhibited by cardioactive glycoside, ouabain. The alterations in level of this enzyme were followed in spleen lymphocytes and hippocampus prepared from rats. Detection of Na+ /K+ ATPase has been made by western blot analysis using primary antibodies oriented against α subunit of Na+ /K+ ATPase. Studies of lymphocytes were based on usage of both monoclonal and polyclonal antibodies. In studies of hippocampus monoclonal antibodies were used. The first aim of my work was to determine the alterations in the level of Na+ /K+ ATPase in spleen lymphocytes cultivated in tissue culture (i.e. under in vitro conditions) in the presence of morphine or strong mitogen, concanavalin A (ConA). The second aim of these theses was to determine the changes of Na+ /K+ ATPase α subunit in hippocampus of rats, which were under in vivo conditions exposed to stress lasting 3 days. The stress of experimental animals was induced by deprivation from sleep. The long-term incubation of spleen lymphocytes with 10 μM morphine for 48 hours did not cause a significant change of Na+ /K+ ATPase α subunit level. This result was obtain by analysis of post nuclear fraction (PNS), by use of monoclonal...
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Role of hippocampal neurons in creation of cognitive schemas and higher-order spatial relationships
Lebedeva, Maria ; Kelemen, Eduard (advisor) ; Kopřivová, Jana (referee)
The hippocampus is the key structure in formation of representations of space (cognitive maps) in rats. Formation of spatial representations of simple environments has been described in details, in this work we focused on emergence of a spatial map of a complex environment from individual simple maps. A radial-arm maze was used to model a complex environment, where each arm was surrounded by unique pattern of proximal visual landmarks. Long Evans rats were allowed to explore gradually four different arms of the maze in a sequence of three sessions. During the first and second sessions rats separately visited two novel pairs of neighboring arms (arms 1 and 2 in the first session, arms 3 and 4 in the second session). In the third session rats were exposed to a new combination of already familiar arms (arms 2 and 3) to study how the two hippocampal maps, acquired originally as independent of each other, are integrated as the rat learns about their spatial relationship. Rats were exposed to this sequence of three sessions twice - before and after sleep. The activity of hippocampal neurons was recorded using a microelectrode system during the maze exploration and sleep. Our first observations suggest that representation of a complex environment neither is a simple combination of preexisting individual...
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The establishment of invariable behaviour of rats in novel one-trial trace association task (OTTAT)
Alexová, Daniela ; Stuchlík, Aleš (advisor) ; Telenský, Petr (referee)
Animal episodic-like memory tasks represent important component of episodic memory research. However, currently available episodic-like memory tasks are not based on episodic-like memory or encompass important caveats. In our laboratory, we recently devised a novel one-trial trace association task (OTTAT) to examine one-time associations of temporally discontinuous stimuli. This thesis deals with the improvement of OTTAT protocol by rat strain and compartment divider ('doors') selection which optimally promote the establishment of invariable behaviour of rats in OTTAT. Moreover, the accuracy of one-trial associations is also assessed by determining specificity of "rapid escape" response to conditioned stimulus of given sound characteristics. In Experiment 1, rats (Sprague-Dawley (SD), n = 36; Wistar (WI), n = 17; Long-Evans (LE), n = 8) were habituated 15 min daily for 3 days with standard doors (9 x 11 cm opening) to modified light and dark apparatus. The number of transfers between compartments and values of time spent in dark compartment obtained from 3rd habituation session were evaluated as indicators of invariable behaviour of rats. We found WI rats spend significantly more time in dark compartment than LE (p = 0.002) and SD rats (p = 0.001) and have significantly fewer transfers than LE rats...
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Memory consolidation of mental schemas during sleep
Hanzlík, Adam-František ; Kelemen, Eduard (advisor) ; Janíková, Martina (referee)
A core feature of the human mind is the ability of abstraction. Relying on this ability, a mental or cognitive schema is a memory framework which underlies alike memory representations. In order for newly acquired memory representations to be preserved for long-term storage, they have to undergo memory consolidation and sleep is a major factor in this process. In a rat model, learning in the context of an existing schema is faster and it is characterised by IEG up-regulation. It is presumable that consolidation during sleep enables the extraction of commonalities from alike memory representations, resulting in schema formation. On a mechanistic level, schemata might be formed by a process which (a) employs synaptic potentiation induced by neuronal replay, (b) requires synaptic downscaling and (c) affects overlapping memory representations. This overlapping character of schema creation might be reflected by the nature of neuronal replay in the hippocampus. It appears that individual sleep stages influence schemata consolidation differently. In human experiments on schemata consolidation, the amount of knowledge a participant is given prior to training is critical.
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Neuronal mechanisms of consolidation of memories for behavioral episodes in sleep
Petránová, Erika ; Kelemen, Eduard (advisor) ; Telenský, Petr (referee)
Memory is an important ability of an individual allowing efficient operations with information acquired during lifetime. Memory is a dynamic process consisting of different phases such as encoding, consolidation and repeated retrieval of the memory. Received information from surrounding environment travels to the short-term storage, from which, in certain amount of time after re-evaluation of its relevance, it is decided about its transport to structures designated for long-term storing. The mechanism used for this transformation is referred to as consolidation. Consolidation occurs on systematic and synaptic level. Positive strengthening effect on memories coded right before sleep has been observed many years ago. The role of sleep in the consolidation of memory representation is still unknown, though there are multiple hypotheses that stress different points of view on the consolidation process. In the last few decades sleep has been given an active role in this process. An interesting problem regarding sleep consolidation is not only the mechanism, but also the preference of a specific type of memory that is being consolidated during sleep. During examination of consolidation of declarative memory, we can observe, in case of episodic memory, an improvement of mainly space-time association...
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Disruption of hippocampal-prefrontal connection in animal models of schizophrenia
Černotová, Daniela ; Svoboda, Jan (advisor) ; Moravcová, Simona (referee)
Schizophrenia is a heterogeneous mental disease that afflicts about 1% of population with no treatment available that would ameliorate all of its symptoms. The key structures affected in schizophrenia are the hippocampus and the prefrontal cortex. This work focuses on the interplay between these structures and on the monosynaptic hippocampal-prefrontal connection, the abnormal neural activity of which is the main cause of cognitive, positive and negative symptoms of schizophrenia. This work summarizes existing findings about both normal and impaired function of the hippocampal-prefrontal connection and provides an overview of animal models frequently used in research. Key words: hippocampus, prefrontal cortex, schizophrenia, interneuron, animal model
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Gene expression pattern in the adult brain of the experimental rat after prenatal exposure to methamphetamine
Tomášková, Anežka ; Černá, Marie (advisor) ; Rudá, Jana (referee)
Introduction: Methamphetamine is a drug frequently taken by drug-addicted pregnant women and happens to be one of the most commonly used drugs in the Czech Republic. This drug passes easily through a placental barrier into the fetus. Thus it can negatively affect not only the mother but also the prenatal development of her offspring. Objectives: This research aims to provide a general screening of gene expression in selected regions of the F1 generation of the brain prenatally affected by methamphetamine, to verify whether exposure to methamphetamine affects the generation of offspring of exposed females at the level of gene expression in selected regions of the brain, and to valuate possible changes in gene expression. Methods: In selected parts of the brain, collected from a rat, the microarray hybridization and the real-time PCR were set to evaluate express changes in the expression of selected genes. Results: Statistical analysis of the microarray hybridization did not show a significantly altered gene expression in the tested genes. Only boundary values for 13 genes were measured, which were further tested by the real-time PCR. After a statistic evaluation of the real-time PCR, the significantly altered expression was found in 2 genes. The notably changed expression of DRD3 and TACR3 genes...
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Prenatal exposure to methamphetamine and its effect on the gene expression in the selected parts of the brains of experimental rats
Tomášková, Anežka ; Zoubková, Hana (advisor) ; Rudá, Jana (referee)
Introduction: Methamphetamine is a drug frequently abused by drug-addicted pregnant women and also one of the mostcommonly used drugs in the CzechRepublic. This drug passes easily through a placental barrier into the fetus. Thus it can negatively affect not only the mother but also the prenatal development of her offspring. Objectives: In the framework of the grant project GA CR: 14-03708S, the long-term effects of prenatal exposure to methamphetamine were detected. It was determined whether the prenatal methamphetamine exposure affects the generation of offspring of exposed females at the level of gene expression of genes in specific regions of the brain, striatum, hippocampus and prefrontal cortex. Methods: In the selected parts of the brain, which were removed from the rat, the microarray hybridization and the real-time PCR to express changes in expression of selected genes were performed. Results: Statistical analysis of microarray hybridization did not show the significantly altered gene expression in tested genes significantly. Only boundary values for 13 genes were measured, which were further tested by real-time PCR.After a statistic evaluation of real-time PCR, the significantly altered expression was found in 2 genes. The significantly changed expression of DRD3 and TACR3 genes was found...
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The influence of inflammatory cytokines on depressive disorders
Svobodová, Eva ; Bendová, Zdeňka (advisor) ; Krulová, Magdaléna (referee)
1 Abstract Depressive disorders are one of the three most frequent diseases causing disability of everyday life of humans. Its occurrence in the population is rapidly increasing. Etiology of depression is unclear, and the treatment usually only ameliorates its symptoms. In patients, there were identified signs not only of chronic stress, which has been associated with depression for quite a long time, but also signs of chronic inflammation in the body. This has led to focusing on proinflammatory cytokines and their connection to chronic stress and depressive symptomatology. We are also interested in the causal link between pro-inflammatory markers and stress that has not yet been unequivocally clarified. The aim of this study is to combine the knowledge about the influence of chronic stress on the development of depressive disorder gained from animal and human models. Additionally, to combine the knowledge of the effect of specific proinflammatory cytokines on the development of the depressive disorder and the change in brain structures morphology which may underlie the symptoms of this disease.
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