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Stress markers and methodologies for their measurement in selected model species
Langmajerová, Anna ; Nekovářová, Tereza (advisor) ; Petrásek, Tomáš (referee)
The stress response is a cascade of physiological and subsequently behavioural processes that enable the organism to cope with various stressful situations and influences (stressors). The manifestations of stress in different organisms are to some extent similar, but at the same time they may differ in intensity and manner. Stress can be measured using biological markers, which are objective and measurable and indicative of underlying biological processes. This bachelor thesis focus on stress markers and the methodology of their measurement. It also discusses specific types of stress markers in each model, for example, measurement of stress hormones (cortisol, corticosteroid), measurement of body temperature, blood pressure or heart rate, or behavioural performance. The thesis also focus on the issue of suitability and applicability of various methods of measuring and evaluating stress in individual models, depending on their accuracy and welfare of the animals during a given measurement, which may influence the test results. Keywords: animal model, behavior, biomarker, stress
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Vasa vasorum of the coronary arteries in an animal heart model
Patzelt, Matěj ; Stingl, Josef (advisor) ; Laichman, Stanislav (referee) ; Slížová, Dáša (referee)
The vasa vasorum of the coronary arteries is a system of tiny vessels that nourish the wall of the coronary arteries. Recently, the vasa vasorum has been attributed importance in the pathogenesis of atherosclerosis, necrosis of the tunica media, or in excessive healing of the intima after stenting. The vasa vasorum system is described in detail on pathologically altered hearts, however, studies that would deal with a detailed description on a healthy human heart or on its animal model are minimal. The aim of the dissertation was to describe the structure and origin of the vasa vasorum of the coronary arteries on an animal model of the heart of a pig, to describe the history of the term vasa vasorum and possibly to describe secondary findings on the examined samples. A total of 36 healthy pig hearts were used in the study. Part of them was injected with India ink through the ostium of the coronary arteries and subsequently histologically processed, other hearts were directly fixed in toto in formalin and histologically processed, the remaining part of the hearts was injected through the ostium of the coronary arteries with mercox resin and then corrosive casts of the coronary arteries were created. These samples were evaluated using a scanning electron microscope. Histological processing of the...
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Cognitive, structural and functional brain changes in a model of psychotic relapses
Ledvinková, Michaela ; Nekovářová, Tereza (advisor) ; Telenský, Petr (referee)
Schizophrenia is a serious nerodevelopmental disease with many sophisticated symptoms. One of its characteristics are relapses which are currently surrounded by consensus that each relaps causes further structural and functional defecits and can even lead to loss of grey matter. Recently, studies of cognitive deficit became prominent and increased the number of possible methods to study schizophrenia. Animal models are used for studying this phenomenon and focuses on neurobiological processes and cellular metabolism and its research is crucial to developing new ways of treatment and understanding schizophrenia. This review mainly focuses on relapses and how they affect progression of this desease. Key words: schizophrenia, psychosis, relaps, neurobiological progression, energy metabolism, cognitive deficit, animal models
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The potential of psychedelics in the treatment of drug addiction in animal models.
Mallarino, Barbara ; Šíchová, Klára (advisor) ; Honc, Ondřej (referee)
Psychedelics are mind-altering and perception-changing psychoactive compounds that can produce some significant changes in the ordinary wiring of the brain. Substantial attention is paid to some of the most promising compounds for addiction and mental health research: LSD, tryptamines (psilocybin, DMT) and ibogaine. The underlying neurobiological basis of the development of addiction and relevant animal models and methods are described in the first part. Following, changes in brain regions connectivity induced by psychedelics and molecular mechanisms of action are discussed, emphasising the potential anti-addictive properties. The last part of the thesis focuses on data acquired from preclinical animal studies, which helps to further understand some of the mechanisms underlying their effectiveness in the clinical treatment of drug addiction.
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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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Cloning, expression and biochemical characterisation of mouse glutamate carboxypeptidase II.
Knedlík, Tomáš ; Konvalinka, Jan (advisor) ; Vaněk, Ondřej (referee)
English Abstract Glutamate carboxypeptidase II (GCPII) is a membrane metallopeptidase expressed in many human tissues, predominantly in prostate, brain and small intestine. In brain it cleaves the most abundant peptide neurotransmitter N-acetyl-L-aspartyl-α-L-glutamate into N-acetyl-L-aspartate and free L-glutamate. Thus, GCPII participates in glutamate excitotoxicity through the release of free glutamate into the synaptic cleft. Inhibition of this activity has been shown to be neuroprotective in rats. In the human jejunal brush border, GCPII cleaves off terminal glutamate moieties from poly-γ-glutamylated folates, which can be then transported across the intestinal mucosa. The function of GCPII in human prostate is unknown but it is overexpressed in prostate cancer. Therefore, GCPII is an important marker of prostate cancer and its progression.Moreover, it could become a perspective target for treatment of prostate cancer as well as neuronal disorders associated with glutamate excitotoxicity. For the development and testing of novel drugs and therapeutics it is necessary to have an appropriate animal model. Mouse (Mus musculus) is such a model and it is widely used by many experimentators. However, no detailed comparison of mouse and human GCPII orthologs regarding their enzymatic activity, inhibition...
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Animal models of obsessive-compulsive disorder
Radostová, Dominika ; Stuchlík, Aleš (advisor) ; Kopřivová, Jana (referee)
Obsessive compulsive disorder (OCD) is a widespread chronic psychiatric disorder, presenting itself with a wide range of symptoms. The heterogenity of OCD manifestations hinders the resarch and the interpretation of acquired results. Clinical studies are complemented by new insights collected from studies of animal models of OCD, which are nowdays integral to the resarch of OCD. During the course of the resarch many genetic, behavioral and pharmacologic animal models were developed. Number of works were not worked on further, however some models had been studied for a long time. Evaluation of individual models is dependant on many factors, and therefore the degree of validity and suitability for resarch differs between them. Powered by TCPDF (www.tcpdf.org)
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Monitoring of the development of the Huntington's disease in transgenic minipigs with N-terminal part of human mutated huntingtin: biochemical and motoric changes of F0, F1 and F2 generation
Kučerová, Šárka ; Ellederová, Zdeňka (advisor) ; Klempíř, Jiří (referee)
Huntington's disease (HD) belongs to neurodegenerative disorders. It is a monogenic disease caused by trinucleotic CAG expansion in exon 1 of gene coding protein huntingtin. Even though the cause of HD is known since 1993, the pathophysiology and cure for HD reminds to be found. The animal models are being used for better understanding of HD. The most common animal models for HD are rodents, especially mice but it was also important to create large animal models, which will be more like human. Therefore, TgHD minipig was created in Academic of Science in Liběchov in 2009. This model was created by microinjection of lentiviral vector carrying N-terminal part of human HTT with 124 repetitive CAG in exon 1. This model is viable and in every generation, is part of the offspring transgenic. In this thesis, I specialized to biochemical and behavioral changes of this model. I compared transgenic and wild type siblings. I found that biochemical changes are manifested mostly by increased level of mtHtt fragments in testes and brain. In behavioral part of this thesis I established new methods for testing behavioral changes in this model. The introduced methods showed some changes between wild type and transgenic animals at the tested ages but these changes were not significant due to the low number of...
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Acute effects and addictive potential of new synthetic drugs from cathinone group - an animal study
Danda, Hynek ; Páleníček, Tomáš (advisor) ; Kubešová, Anna (referee)
Novel psychoactive substances (NPS) are a novel problem of the drug scene. NPS mimic effects of the "classic" illicit drugs, but since they have a different chemical structure, they are usually not covered by legislative control. The exact nature of the aforementioned effects depends merely on the description by users, with a proper scientific assessment still absent. Aim of this study is to evaluate effects and addictive potential of naphyrone (a derivative of cathinone) in Wistar rats. High concentration of naphyrone in the brain tissue discovered by pharmacokinetic analysis proved its high blood-brain barrier permeability. Brain level of naphyrone peaked at approximately 30 min after the treatment, nearly at the same time as in the serum. Since naphyrone administration significantly rises body temperature and increases overall locomotion, its stimulant effect is prominently apparent. Our study failed to prove any effect of naphyrone on sensorimotor gating. Tendency to produce conditioned place preference was observed but was not significant. My thesis reports on initial and novel findings about impact of naphyrone administration on physiological parameters of the animal model.
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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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