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Effect of dizocilpine on behavioral strategies of rats in the place avoidance task
Antošová, Eliška ; Valeš, Karel (advisor) ; Frynta, Daniel (referee)
Non-competitive antagonists of NMDA receptors can induce psychomimetic effects - they can cause schizophrenia-like behavior in healthy volunteers. MK-801 is such an agent. It is often used to model schizophrenia-like behavior in experimental animals. On the other hand, non-competitive antagonists of NMDA receptors show antidepressant effects both in patients suffering from depression and in animal models. Currently, cognitive deficit is considered to be a crucial symptom of the schizophrenia. Cognitive coordination is a process distinguishing irrelevant and relevant stimuli. A disruption of this process could play a pivotal role in cognitive deficit in schizophrenia. Active Allothetic Place Avoidance task (AAPA) could be a useful tool to study this phenomenon. In this task an animal has to distinguish between two spatial (reference) frames, whereas one of them is irrelevant and the other is relevant. The aims of my diploma thesis were: to study 1) behavioral strategies of laboratory rats in AAPA task and 2) effect of MK-801 on behavioral strategies and cognitive efficiency of rats in this task. The rats demonstrated two different strategies in the AAPA task. The first strategy was an active avoidance of an aversive sector; the second one was "freezing" with minimal active movement on the arena. Application...
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The role of main excitatory and inhibitory transmitters in epileptic seizures and the effect of antiepileptic drugs in the immature brain
Liptáková, Soňa ; Mareš, Pavel (advisor) ; Komárek, Vladimír (referee) ; Šlamberová, Romana (referee)
Epilepsy affects 50 million people worldwide. Approximately 50% of epilepsies start in the infancy and childhood. In addition, there are several age-bound epileptic syndromes which are difficult to treat. Due to these facts, developmental studies of epileptic seizures are of primary importance. Predominance of excitation over inhibition is a mechanism of nearly all types of epileptic seizures. Hypothesis that this compromised balance can be normalized by drugs affecting main excitatory and inhibitory system at different stages of brain development was tested in models with different pathogenesis. Our studies demonstrated that seizures induced by derrangement of GABAergic inhibition can be suppressed by antagonists of NMDA receptors (MK-801) and vice versa seizures with glutamatergic pathogenesis can be affected by drugs potentiating GABAergic system (valproate, ganaxolone) at all developmental stages in immature rats. Analysis of site of action of NMDA receptor antagonists demonstrated reciprocal function of anterior and posterior parts of substantia nigra, structure important for spread of epileptic activity to spinal cord. Special attention was given to an age-dependent model - flexion, emprosthotonic seizures elicited by administration of NMDA. Valproic acid, which potentiates GABAergic inhibition,...
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Sepsis in newborne
Baláčková, Šárka ; Voxová, Barbora (advisor) ; Paterová, Pavla (referee)
Author: Šárka Baláčková Title: Septic states of newborns Bachelor thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Field of study: medical laboratory technician Background: The aim of the work was to sample information on the issue of septic states of newborns, to describe laboratory diagnosis of examining neonatal sepsis. To map rate of the most common pathogens causing this illness in Masarykova hospital in Ústí nad Labem. Method: Tracking of sampled blood cultures at neonatal department between years 2011- 2015. Comparison of total amount of blood cultures with the amount of positive blood cultures and the rate of particular pathogens causing neonatal sepsis. Results: During the reporting period were collected a 5271 blood cultures to total count. 1047 of those were positive, making it 20 %. The most prominent causes of neonatal sepsis is above all coagulase-negative Staphylococcus with the count of 801 occurrences, which is 76,5 %. Followed by Gram-negative facultative anaerobic rods with 103 occurrences (10,8 %), Anaerobic bacteria with 48 counts (4,6 %), Enterococcus species with 31 counts (3%), Staphylococcus aureus with 26 counts (2,5 %), Streptococcus species with 21 counts (2 %) and Yeasts with 7 counts (0,7 %). Conclusions: Neonatal septic state is a serious...
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Identification of the binding sites on transient receptor potential cation channel TRPC6 for Calmodulin and S100A1
Bílý, Jan ; Teisinger, Jan (advisor) ; Krůšek, Jan (referee) ; Pavlíček, Jiří (referee)
Identification of the binding sites on transient receptor potential cation channel TRPC6 for Calmodulin and S100A1 The TRP (transient receptor potential) group of ion channels represents a large subset of membrane receptors. A part of this supergroup are canonical TRPC channels with a sequence homology analogical to TRP receptor first discovered at fruit fly (Drosophila melanogaster). These membrane channels are involved in a variety of physiological functions in different cell types and tissues. TRPC6 is a non-selective cation channel that modulates the calcium level in eukaryotic cells (including sensory receptor cells) in response to external signals. TRPC6 channel contains binding domain CIBR (Calmodulin inositol binding region), which is also able to adapt to calcium binding protein S100A1. Characterisation of the integrative binding site for calmodulin (CaM) and S100A1 at the C-tail of TRPC6 is presented in this work. Using site-directed mutagenesis, soluble protein fragments TRPC6 CT (801-787) were prepared with intentional changes in amino acid sequence. Several positively charged amino acid residues (Arg852, Lys856, Lys859, Arg860 and Arg864) were determined by measurement of fluorescence anisotropy influence and their participation in the calcium-dependent binding of CaM and/or S100A1 to...
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Separation of hippocampal function in Morris water maze and in active place avoidance by alternance protocol
Vojtěchová, Iveta ; Petrásek, Tomáš (advisor) ; Hiadlovská, Zuzana (referee)
In this work, we examined the executive functions of the hippocampus at the behavioral level as a so-called behavioral separation in adult rats. We studied an impact of day-to-day alternation versus sequential learning (and the order of learning) of two spatial tasks (Morris Water Maze and Active Allothetic Place Avoidance) testing different hippocampal functions (experiment 1), or an impact of sequential versus alternating learning of one task (Active Allothetic Place Avoidance) in two different rooms (experiment 2), on performance. We found out that rats are able to learn both tasks as well as to discriminate between the two contexts regardless of the order or alternating of learning. Because such executive functions are impaired in human patients suffering from schizophrenia, we used this procedure also in the rat model of schizophrenia induced by acute intraperitoneal application of dizocilpine (MK-801), glutamate NMDA receptors antagonist, in the dose of 0.08 mg/kg. We failed to selectively disrupt the behavioral separation, however, we observed general learning deficit and hyperlocomotion regardless of the alternation in the Active Allothetic Place Avoidance task in these rats. The cognitive impairments in connection with learning after such low dose of MK-801 in this task have not yet been...
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The effect of agonist of the metabotropic glutamate receptors LY 379268 in an animal model of psychosis
Rišňovská, Dominika ; Stuchlík, Aleš (advisor) ; Telenský, Petr (referee)
Introduction: Schizophrenia is a neuropsychiatric illness characterized by impairments in cognition and positive and negative symptoms. As currently used antipsychotics do not treat all symptoms of the disease, further research of the therapeutic potential of various drugs in the treatment of this disease is crucial. Psychosis is a condition or a mental state that usually accompany schizophrenia, as well as other disorders. We used MK-801, a non-competitive antagonist of NMDA receptors to induce an experimental model of psychosis in rats. By binding to the NMDA subtype of glutamate receptors located on inhibitory interneurons, MK-801 has been shown to elicit an overactivation of cortical and hippocampal pyramidal neurons, leading to behaviors such as hyperlocomotion, stereotypy or cognitive impairments. LY 379268, an agonist of group II metabotropic glutamate receptors, binds to both presynaptic and postsynaptic receptors on pyramidal neurons. It has been suggested that it could alleviate the MK-801-induced hyperactivity of the principal neurons. In this study, we sought to demonstrate the effects of LY 379268 in the MK-801 animal model of psychosis and hypothesized that LY 379268 will ameliorate deficits in the reversal learning induced by MK-801. Materials and methods: Long Evans rats received...
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The use of tryptophan depletion in the study of the mechanism of action of psychopharmaceuticals
Jirásková, Markéta ; Valeš, Karel (advisor) ; Telenský, Petr (referee)
Tryptophan depletion is a non-pharmacological and non-invasive method extensively used to investigate the role of serotonin (5-hydroxytryptamine in humans and animals. The method is based on reducing the availability of the essential amino acid tryptophan, the dietary serotonin precursor. As a precursor of serotonin, L-Tryptophan has a key role in the regulation of many physiological processes and, inter alia, in the pathology and pathophysiology of neuropsychiatric disorders and diseases. Despite the fact, that the method of tryptophan depletion has been applied in many experimental studies, the exact mechanism, by which tryptophan depletion inducted neurophysiological effects, remain unclear. Also, the protentional use of this method together with other drug coadministration has not been explored in detail yet. In this thesis, the most possible mechanisms of tryptophan depletion are discussed. Biochemical and behavioural effects of low dose of dizocilpine (0.1 mg/kg and 0.15 mg/kg) in animal model of tryptophan depletion are investigated as well. And finally, effects of administration of allopregnanolone and tacrine in model of tryptophan depletion with coadministration of MK-801 are studied. The results show that acute tryptophan depletion with prior starvation, not chronic depletion, caused...
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Spatial memory in humans and its disorders: From animal models towards schizophrenia
Fajnerová, Iveta ; Vlček, Kamil (advisor) ; Rokyta, Richard (referee) ; Jiruška, Přemysl (referee)
Spatial memory is often studied using spatial tasks originally developed for animals, such as the Morris water maze and the Carousel maze tasks. Both tasks have an important role in the process of identification of brain areas crucial for spatial memory, and also in pharmacological research of animal models of neuropsychiatric diseases. In recent years considerable attention has been devoted to the research and treatment of cognitive impairment in schizophrenia. Comparative research addressing cognitive abilities of both animals and patients in similar tasks, could therefore lead to verification of the predictive and face validity of animal models of this complex disorder. The aim of this study was to create virtual analogues of these tasks, which would allow this comparative approach. This thesis first describes the experiment testing the performance of an animal model of schizophrenia induced by the application of dizocilpine (MK-801) in reversal version of both mentioned spatial tasks, in order to assess mental flexibility and learning abilities affected in schizophrenia. Other two experiments present the findings of the two virtual analogues tested in the first episode of schizophrenia patients. Our results confirm the presence of deficits in spatial memory and mental flexibility, functions dependent on...
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Neuropharmacology of spatial navigation, cognitive coordination and flexibility tests in animal models
Prokopová, Iva ; Stuchlík, Aleš (advisor) ; Vyklický, Ladislav (referee) ; Blahoš, Jaroslav (referee)
Spatial navigation, cognitive coordination and behavioral flexibility belong amongst cognitive functions, which play a role in many neuropsychiatric disorders. Behavioral tasks have proved to be useful paradigms to test these functions in pharmacological or genetic animal models. First aim was to determine a potential interaction between β-adrenergic and α1-adrenergic or D2-dopaminergic systems. Spatial navigation and coordination were impaired in both studies during co-aplication of subthreshold doses of drugs. Used substances belong to group of widely prescribed drugs, thus our results could be implicated in clinical practice. Another study examined an acute effect of MK-801 (animal model of schizophrenia) on behavioral flexibility in Carousel maze and the Morris water maze (MWM). Carousel maze showed higher sensitivity with impairments from 0.08 mg.kg-1 compared to 0.10 mg.kg- 1 in MWM. The final experiment aimed at testing the effect of reduced expression of Nogo-A protein on spatial navigation and behavioral flexibility of rats. A battery of tests in the Carousel maze revealed impairment in cognitive functions, MWM showed unaffected working memory of rats. Our results support the hypothesis linking Nogo-A knock-down rats with neuropsychiatric symptoms and cognitive disorders. Key words:...
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The effect of agonist of the metabotropic glutamate receptors LY 379268 in an animal model of psychosis
Rišňovská, Dominika ; Stuchlík, Aleš (advisor) ; Telenský, Petr (referee)
Introduction: Schizophrenia is a neuropsychiatric illness characterized by impairments in cognition and positive and negative symptoms. As currently used antipsychotics do not treat all symptoms of the disease, further research of the therapeutic potential of various drugs in the treatment of this disease is crucial. Psychosis is a condition or a mental state that usually accompany schizophrenia, as well as other disorders. We used MK-801, a non-competitive antagonist of NMDA receptors to induce an experimental model of psychosis in rats. By binding to the NMDA subtype of glutamate receptors located on inhibitory interneurons, MK-801 has been shown to elicit an overactivation of cortical and hippocampal pyramidal neurons, leading to behaviors such as hyperlocomotion, stereotypy or cognitive impairments. LY 379268, an agonist of group II metabotropic glutamate receptors, binds to both presynaptic and postsynaptic receptors on pyramidal neurons. It has been suggested that it could alleviate the MK-801-induced hyperactivity of the principal neurons. In this study, we sought to demonstrate the effects of LY 379268 in the MK-801 animal model of psychosis and hypothesized that LY 379268 will ameliorate deficits in the reversal learning induced by MK-801. Materials and methods: Long Evans rats received...
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