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Mitochondrial dysfunctions in depression
Javorská, Jana ; Stuchlík, Aleš (advisor) ; Kolář, David (referee)
Depression (major depressive disorder; MDD) is a common and chronic psychiatric disorder. MDD causes a significant reduction in the quality of life, reduces the ability to work, and thus causes a burden on disabled patients, healthcare, and all of society. The pathophysiological features of depression are often ambiguous, and therefore current treatment for depression is insufficient. Chronic stress plays an important role in the pathogenesis of depression. It causes dysregulation of the hypothalamic-pituitary-adrenal axis (HPA axis) controlling cortisol release, imbalance of neurotransmitters and neuromodulators, and imbalance between pro- inflammatory and anti-inflammatory cytokines. Another neurobiological sign of depression is a disruption of energy metabolism in the brain, for which mitochondria are responsible. In addition to ATP, mitochondria also form reactive oxygen species (ROS). ROS are in excessive amounts during chronic stress and disrupt cellular energy. Therefore, substances related to mitochondrial energy and antioxidant effects are currently being investigated. Ketamine, dizocilpine and phencyclidine are particularly effective in mitochondrial metabolism. However, the clinical use of these substances is complicated by their hallucinogenic and neurotoxic effects. Antioxidants help...
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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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Age related changes in the central auditory system in the laboratory rat
Burianová, Jana ; Popelář, Jiří (advisor) ; Stuchlík, Aleš (referee) ; Rokyta, Richard (referee)
Age-related hearing loss, presbyacusis, is becoming one of the most common health disabilities in elderly people. Despite intensive research, age-related changes are still poorly understood and, given the continuous aging of the population, it is desirable to improve our knowledge of the mechanisms of presbyacusis. Consequently we decided to study age-related changes that appear in the structure and function of the central auditory system in the brain of experimental animals. In the first experiment we tested the hypothesis that during aging there is substantial decline of GABA-mediated inhibition in the central auditory system of the rat. We evaluated levels of both isoforms of glutamatedecarboxylase (GAD65, GAD67), a key enzyme in GABA synthesis. Western blot analysis revealed an overall decrease in levels of both isoforms in the inferior colliculus as well as the auditory cortex in aged rats. The same pattern was found when we used immunohistochemistry analysis; there was a decrease in the number of GAD65 and GAD67-ir neuronal bodies and a decrease in the density of the labeling. The results were similar for both GAD isoforms and both studied strains - the normally aging Long Evans strain (LE) and the Fischer 344 (F344) strain known for accelerated aging. In the next experiment we evaluated...
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Learning and memory in Nogo-A knockdown rats
Petrásek, Tomáš ; Stuchlík, Aleš (advisor) ; Zach, Petr (referee) ; Rokyta, Richard (referee)
The Nogo-A protein belongs among the most important regulatory molecules in the brain, regulating development of neuronal and glial cells, axon guidance and adult synaptic plasticity. Although it has been studied mainly as an obstacle to axon regeneration after CNS injury, it plays a role in many pathological conditions, including neurodegenerative and neuropsychiatric diseases. This work offers a literature review of the current knowledge about functions of Nogo-A and related proteins, and then recapitulates the results of experiments focused on the impact on decreased expression of Nogo-A on behavior in a transgenic rat model. The most important finding is that the Carousel Maze performance, tapping higher cognitive functions such as cognitive coordination and cognitive flexibility, is remarkably impaired in this model, while other cognitive functions, such as spatial navigation and both spatial and non-spatial memory are spared in the Nogo-A deficient rats. The results are discussed in the context of a hypothesis linking Nogo-A mutations or abnormal expression to human schizophrenia. We conclude that the Nogo-A deficient rats constitute a very promising animal model of schizophrenia and deserve further attention. Powered by TCPDF (www.tcpdf.org)
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Hippocampal coding of positions of inaccessible objects
Hrůzová, Karolína ; Stuchlík, Aleš (advisor) ; Kudláček, Jan (referee)
The survival of the animals depends on their ability to memorize locations and to use behavioral spatial navigation strategies. The crucial structure for this type of behavior and memory is the hippocampus, by its ability to create a cognitive map. In this structure, there are specialized pyramidal cell called place cells. They respond by their complex firing pattern to specific animal's location in the environment. Even though many studies have investigated the role of hippocampal pyramidal cells in spatial navigation and object position discrimination, their function during inaccessible object position discrimination is not yet clarified. In our experiment, rats were trained in a behavioral task to discriminate between rewarded and nor- rewarded positions of object located in an inaccessible space. We investigated the role of individual hippocampal cells during this task by single neuron electrophysiology. The first aim of this study was to decide which of two configurations of objects presented on a computer screen during spatial object discrimination task rats can discriminate easily. The second aim is to show whether and how information about the position of inaccessible objects is represented in the hippocampus using single-neuron electrophysiology. We found out, that animals did not reach...
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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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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 role of the Wnt signaling pathway in the regeneration following ischemic brain injury
Kriška, Ján ; Anděrová, Miroslava (advisor) ; Stuchlík, Aleš (referee) ; Zíková, Martina (referee)
The role of the Wnt signaling pathway in the regeneration following ischemic brain injury Focal cerebral ischemia results in the loss of neural cells, which may cause permanent disability. At the same time, there are precursor cells (neural stem/progenitor cells and NG2 glia) that naturally reside in the postnatal brain and may proliferate and give rise to other cell types. Their fate is to a large extent influenced by morphogens of the Wnt and Shh family. However, the role of these cellular pathways in differentiation of precursor cells is still enigmatic. For this reason, we employed transgenic mice that enabled us to inhibit or hyper-activate the canonical Wnt signaling pathway, or to map the fate of NG2 cells. The induction of ischemia was achieved by the occlusion of the middle cerebral artery. The changes in the differentiation potential were characterized at the mRNA, protein, and functional levels. First, we evaluated neural stem/progenitor cells isolated from neonatal mice under physiological conditions and found out that Wnt signaling promotes neurogenesis and suppresses gliogenesis. Next, we focused on adult mice and detected a smaller impact of Wnt signaling on their differentiation potential. Nonetheless, its effect was more profound after the induction of ischemia, as we identified...
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BUILDING OF TWO BLOCKS IN THE CITY MONUMENT RESERVATION IN JIHLAVA
Zima, David ; Stuchlík, Aleš (referee) ; Havliš, Karel (advisor)
The subject of this bachelor's thesis is an urban and architectural study of the completion of two rehabilitated blocks in the historic center of Jihlava. In the solved area there is an intertwining of two districts with predominant functions - work and housing. The design works with the urban context of the development of the historic center. Mass regulation and a functional solution of a new development is proposed, which closes both disturbed blocks. The development of the northern block is addressed in detail in the architectural study of four independently functioning buildings - two apartment buildings, an office building and a parking house in the courtyard. The apartment building connected to the existing development is further elaborated in technical and architectural detail. Part of the design is also the solution of the chamber public space newly defined by the proposed development.
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BUILDING OF TWO BLOCKS IN THE CITY MONUMENT RESERVATION IN JIHLAVA
Přibyl, Jan ; Stuchlík, Aleš (referee) ; Havliš, Karel (advisor)
The objective of the bachelor thesis is an urban and architectonic study of two uneffectively used blocks in historical centre of Jihlava. The product is design of built of residential house, public house, parking house and several administrational buildings in context of public space. The design shows concrete solution of the residential house in connection to the public house and parking house.
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