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Analysis of heart rate variability in animal models
Řehořková, Iveta ; Ronzhina, Marina (referee) ; Kolářová, Jana (advisor)
This paper deals with the analysis of heart rate variability (HRV) in animal models. The first part discusses, the basic information concerning the ECG, both in humans and in individual laboratory animals. This is followed by an introduction to the topic of heart rate variability, a description of methods for its determination and the effects of pathologies on HRV values. Prior to the practical section, the methods of ECG acquisition in animal models are discussed, and the function of the perfusion model used in capturing data for this work is also described in detail. The last part deals with the analysis of HRV provided data, performed in Matlab environment and an evaluation of the chosen methods.
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Cognitive flexibility in selected animal models of psychiatric disorders
Janíková, Martina ; Stuchlík, Aleš (advisor) ; Rokyta, Richard (referee) ; Ježek, Karel (referee)
Cognitive flexibility is the ability to adjust thinking and behavior based on changing conditions. Cognitive rigidity has been described in a variety of psychiatric and neurodevelopmental disorders and has been suggested to contribute to symptom maintenance. Therefore, we aimed to study cognitive flexibility and other behavioral characteristics in several rodent models relevant to schizophrenia, obsessive-compulsive disorder, and autism spectrum disorder. In a two-hit mice model relevant to schizophrenia, we found the between-group difference in set- shifting and decreased number of parvalbumin interneurons in the hippocampus of stressed female mice. Interestingly, we found no impairment in any other behavioral task. In two pharmacological rat models relevant to OCD, we showed that sensitization to D2/D3 receptor agonist quinpirole and serotonin 1A/7 agonist 8-OH-DPAT produced severe spatial learning and memory impairment in the Active Allothetic Place Avoidance task. The impairment was so severe that the reversal couldn't be tested. Surprisingly, drugs decreasing glutamatergic neurotransmission, memantine and riluzole, further impaired the performance in both models, although no such effect was observed when they were applied alone. Lastly, we showed that the knockout of a collapsin response...
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Antidepressant potential of serotonergic psychedelics in preclinical research
Dušková, Valentýna ; Vejmola, Čestmír (advisor) ; Skálová, Kateřina (referee)
The treatments for depression available in contemporary medicine have a number of drawbacks. Modern antidepressants, despite fewer side effects than conventional ones, have a slow onset of action and their effectiveness is often individual. Recent studies of psychedelics have indicated their promising to extraordinary potential in the treatment of depression. Clinical research has made significant progress in this direction, as have a growing number of preclinical studies. Psychedelics potentiate signaling pathways and protein expression related to neurogenesis and cell viability and induce an increase in dendritic spines and dendritic branching. At the behavioural level, psychedelics have been shown to attenuate depressive behavioural changes, suppressing anxiety and anhedonia. This paper summarizes the effects of psychedelics in preclinical in vitro and in vivo studies, taking into account the neurobiology of depression, i.e., mainly at the level of neuroplasticity and observed behavioural changes. The first part of the thesis is devoted to the general characteristics of depression and psychedelics, followed by an introduction to preclinical experimental approaches. The central part then describes and discusses individual studies. Keywords: depression; animal models; psychedelics; LSD;...
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Analysis of heart rate variability in animal models
Řehořková, Iveta ; Ronzhina, Marina (referee) ; Kolářová, Jana (advisor)
This paper deals with the analysis of heart rate variability (HRV) in animal models. The first part discusses, the basic information concerning the ECG, both in humans and in individual laboratory animals. This is followed by an introduction to the topic of heart rate variability, a description of methods for its determination and the effects of pathologies on HRV values. Prior to the practical section, the methods of ECG acquisition in animal models are discussed, and the function of the perfusion model used in capturing data for this work is also described in detail. The last part deals with the analysis of HRV provided data, performed in Matlab environment and an evaluation of the chosen methods.
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Effects of early life stress on brain development
Hanišová, Lucie ; Kubová, Hana (advisor) ; Hejnová, Lucie (referee)
Adverse life experience during so called critical developmental periods is known to exert detrimental effects on central nervous system. Early stress may predispose to cognitive impairment, depression or other mental problems as well as to aggravation of existing neuropsychiatric problems. Consequences of early stress are highly age-dependent and affected by sex, genetic predispositions and type of stressor. In addition to prenatal stages, also postpartum period and adolescence are considered as periods of increased sensitivity to environmental disturbances of various origins (chemical, hormonal, physical and particularly social). Utilization of animal models is a direct approach to find out whether exposure to specific stressor alters mental functions and increases risk of behavioral problems. Animal studies also enable to study stress-induced molecular, cellular and structural changes and their role in later development of behavioral alterations.
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Effects of memantine and riluzole on learning deficits in an animal model of obsessive-compulsive disorder induced by 8-OH-DPAT sensitization
Mainerová, Karolína ; Stuchlík, Aleš (advisor) ; Kelemen, Eduard (referee)
Obsessive-compulsive disorder is a chronic psychiatric disease. It seriously limits the quality of life of patients. Treatment of OCD is not yet fully successful and still many patients are left with debilitating symptoms without functioning medication. Animal models of genetic, behavioral, pharmacological, and optogenetic origins are beneficial in the achievement of new understandings of the disease. Chronic sensitization of serotonin 1A and 7-receptors with an agonist 8-OH-DPAT ((8- hydroxy-2-(di-propylamino)-tetralin hydrobromide) induces perseverative and compulsive behaviors, which is considered to constitute an animal model of OCD. In this thesis, the 8-OH- DPAT model has been tested in the active place avoidance task on Carousel maze to provide information about the model on learning. Second, this model is used to determine, whether co- administration of memantine or riluzole alleviates the cognitive and learning deficits of this model. To uncover these effects, an active place avoidance task on a Carousel maze was used. Measured criteria were total distance, entrances to the shock sector, total number of shocks, and median speed after the shock. During habituation, the animals were sensitized to 8-OH-DPAT (with a control group that did not receive 8-OH-DPAT but only saline). In an...
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Effects of Neurotransmission-Modulating Multipotent Compounds in Pharmacological Animal Models of Cognitive Deficit
Chvojková, Markéta ; Valeš, Karel (advisor) ; Kuchař, Martin (referee) ; Rudá, Jana (referee)
In preclinical research on Alzheimer's disease pharmacotherapy, attention is paid to multipotent compounds, enabling intensification of the effect by targeting multiple pathophysiological mechanisms. The aim of the thesis was to assess the effect of multipotent compounds and combination therapy in models of cognitive deficit in the rat. The mechanism of action of the tested compounds was modulation of neurotransmitter systems. The aim of the first part of the study was to compare the effect of experimental monotherapy and combination therapy with an N-methyl-D-aspartate (NMDA) receptor antagonist and a γ-aminobutyric acid type A (GABAA) receptor positive modulator in the trimethyltin-induced model. Superiority of the combination therapy was proven by histological analysis of hippocampal neurodegeneration; however, it did not reach statistical significance in the cognitive test. The other part of the thesis focused on multipotent tacrine derivatives. We demonstrated a positive effect of 6- chlorotacrine-6-nitrobenzothiazole hybrid, as well as 6-chlorotacrine-L-tryptophan hybrid, acting as acetylcholinesterase inhibitors, in the scopolamine-induced model of cognitive deficit. Besides, we demonstrated a low risk of serious side effects of other tacrine derivatives acting as NMDA receptor antagonists....
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Effects of memantine and riluzole on learning deficits in an animal model of obsessive-compulsive disorder induced by 8-OH-DPAT sensitization
Mainerová, Karolína ; Stuchlík, Aleš (advisor) ; Kelemen, Eduard (referee)
Obsessive-compulsive disorder is a chronic psychiatric disease. It seriously limits the quality of life of patients. Treatment of OCD is not yet fully successful and still many patients are left with debilitating symptoms without functioning medication. Animal models of genetic, behavioral, pharmacological, and optogenetic origins are beneficial in the achievement of new understandings of the disease. Chronic sensitization of serotonin 1A and 7-receptors with an agonist 8-OH-DPAT ((8- hydroxy-2-(di-propylamino)-tetralin hydrobromide) induces perseverative and compulsive behaviors, which is considered to constitute an animal model of OCD. In this thesis, the 8-OH- DPAT model has been tested in the active place avoidance task on Carousel maze to provide information about the model on learning. Second, this model is used to determine, whether co- administration of memantine or riluzole alleviates the cognitive and learning deficits of this model. To uncover these effects, an active place avoidance task on a Carousel maze was used. Measured criteria were total distance, entrances to the shock sector, total number of shocks, and median speed after the shock. During habituation, the animals were sensitized to 8-OH-DPAT (with a control group that did not receive 8-OH-DPAT but only saline). In an...
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Mnemonic and behavioural effects of biperiden, an M1-selective antagonist, in the rat
Popelíková, Anna ; Stuchlík, Aleš (advisor) ; Telenský, Petr (referee)
Due to the persisting lack of reliable animal models of cognitive impairment with good translational validity, researches strive to discover new ways and tools to replicate symptoms of human neurodegenerative diseases in rodents. Recently, biperiden, an M1- selective muscarinic antagonist, has been proposed as a potential tool for generating fast screening models of mnemonic deficits such as seen in patients with Alzheimer's disease. Being highly selective for the M1 receptor, a predominant type of muscarinic acetylcholine receptors in the brain involved in cognitive processes, it has been speculated to possibly only influence cognition without causing sensorimotor side effects. Studies assessing the usability of this drug reported conflicting results. We have decided to expand the experimental data and evaluate biperiden's validity in several variants of the Morris water maze. The results of this study showed no significant effect of biperiden on cognitive flexibility, tested by reversal learning. In delayed-matching-to-position paradigm, which tests assesses working memory, we found a difference in performance between the two experimental groups; however, it cannot be unequivocally attributed to a memory impairment. No effects were observed in visible platform task, confirming a lack of...
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Experimental models of ischemic brain injury
Alexová, Daniela ; Valeš, Karel (advisor) ; Alterová, Kateřina (referee)
Title: Experimental models of ischemic brain injury Author: Daniela Alexová Department: Department of Physiology Supervisor: RNDr. Karel Valeš, Ph.D. Abstract: This bachelor thesis focuses on the experimental models of ischemic brain injury closely related to one of the most common forms of brain damage, the ischemic stroke. This type of brain injury is connected to subsequent serious neurological deficits. The studies of experimental models of ischemic brain injury are therefore essential for primary and secondary research. The first two parts of the thesis are dedicated to brief characterization of stroke with focus on types of stroke, incidence, risk factors and molecular mechanism of injury. Next part summarizes the challenges of experimental modeling of ischemic brain injury and the specifics of small and big laboratory animals. The core of the thesis is the description of 11 most frequently used models. Selected models were divided into focal and global models and in each of these categories were furthermore characterized according to procedural performance, animal mortality or success of lesion induction. The key modifications of models introduced during the years in order to increase the reproducibility of brain injury are described as well. All 11 selected experimental models are summarized at the...
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