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Changes of motor performance after epileptic seizure in developing laboratory rats
Hanáková, Helena ; Mareš, Pavel (advisor) ; Stuchlík, Aleš (referee)
The aim of the work was analysis of postictal period - possible changes of motor performance after seizure. Epileptic afterdischarges are induced by stimulation cof ortical sensorimotor area in rat. We will use the intensity to produce human myoclonic seizure in 12-, 18- a 25- days old animals. The youngets and the oldest groups differ by the absence (12-day-old rats) or presence (25-day-old- ones) of postictal refractoriness. Control groups will be formed by intact animals. Individual groups will be observed immidiatelly after seizure and after different intervals. Keywords: epileptic afterdischarge, postictal period, motor performance, laboratory rat, development
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Physiological and pharmacological aspects of tryptophan and serotonin homeostasis in the fetoplacental unit
Karahoda, Rona ; Štaud, František (advisor) ; Stuchlík, Aleš (referee) ; Kacerovská Musilová, Ivana (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate Mgr. Rona Karahoda Supervisor Prof. PharmDr. Frantisek Staud, Ph.D. Title of Doctoral Thesis Physiological and pharmacological aspects of tryptophan and serotonin homeostasis in the fetoplacental unit The placenta is an ephemeral organ inevitable for the successful course of pregnancy. As the main link between the mother and the fetus, the placenta fulfills numerous roles during gestation, including endocrine, transport, and immunoprotective processes. Proper functioning of the placenta is critical for the normal growth and development of the embryo/fetus. Importantly, the latest research has associated perturbations of maternal conditions (such as pharmacotherapy, malnutrition, diseases, stress, or inflammation) with alterations of the trophoblasts' endocrine, transport, and metabolic functions. Of note is the placental utilization of the essential amino acid tryptophan, suggested as a potential mechanism contributing to fetal programming of adulthood diseases. Tryptophan flux along the serotonin and kynurenine pathways generates metabolites with neuroactive, immunosuppressive, and antioxidant properties. Current literature suggests that fine-tuning of tryptophan metabolite concentrations...
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Memory and cognitive coordination impairment in rat models of neuropsychiatric diseases
Vojtěchová, Iveta ; Stuchlík, Aleš (advisor) ; Syka, Josef (referee) ; Hort, Jakub (referee)
The memory and spatial navigation are extremely important brain functions for humans, but they are often the question of life and death for animals. In humans, memory can be disrupted by various neuropsychiatric disorders. The patients suffering from Alzheimer's dementia (AD) have impaired working and long-term memory, spatial navigation, higher cognitive functions and social memory. The deficit of cognitive coordination (the skill to recognize the relevancy of incoming information) and disorientation belong to the symptomatology of schizophrenia. Intelectual disability appears in some patients with autism spectrum disorder. Unfortunately, it is not possible to cure these disorders efficiently because the etiology is not known in the majority of patients. The causes leading to development of these disorders could be revealed using animal models. This thesis contributes to the characterization of the cognitive skills disruptions - as well as other behavioral alterations - in selected rat models of AD (transgenic McGill rat, non-transgenic Samaritan rat) and schizophrenia (lipopolysaccharide model of early postnatal, or prenatal, bacterial infection). The thesis also discusses the validity and limitations of these models. Our results showed a severe deficit of spatial navigation, learning and...
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Molecular mechanism of Cannabinoid receptor 1 regulation by SGIP1
Dvořáková, Michaela ; Blahoš, Jaroslav (advisor) ; Konvalinka, Jan (referee) ; Stuchlík, Aleš (referee)
Molecular mechanism of Cannabinoid receptor 1 regulation by SGIP1 Abstract Src homology 3-domain growth factor receptor-bound 2-like endophilin interacting protein 1 (SGIP1) has been identified as an interacting partner of cannabinoid receptor 1 (CB1R). Their protein-protein interaction was confirmed by co-immunoprecipitation. SGIP1 hinders the internalization of activated CB1R and modulates its signaling in HEK293 cells. Employing whole-cell patch-clamp electrophysiology, we have shown that SGIP1 affects CB1R signaling in autaptic hippocampal neurons. Using a battery of behavioral tests in SGIP1 constitutive knock-out (SGIP1-/- ) and WT mice, we investigated the consequences of SGIP1 deletion on behavior regulated by the endocannabinoid system. In SGIP1-/- mice, exploratory levels, working memory and sensorimotor gating were unaltered. SGIP1-/- mice showed decreased anxiety-like and depressive-like behaviors. Fear extinction to tone was enhanced in SGIP1-/- females. Several cannabinoid tetrad behaviors were altered in the absence of SGIP1. SGIP1-/- males exhibited abnormal THC withdrawal behaviors. SGIP1 deletion also reduced acute nociception, and SGIP1-/- mice were more sensitive to antinociceptive effects of CB1R agonists and morphine. CB1R-SGIP1 interaction results in profound modification of CB1R...
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Calcium signaling of oligodendroglial lineage cells in the animal model of schizophrenia
Kročianová, Daniela ; Anděrová, Miroslava (advisor) ; Stuchlík, Aleš (referee)
Schizophrenia is a neurological disorder with a complex psychopathology, which is far from fully elucidated. In the patients with this disorder, changes on anatomical, cellular, and neurotransmitter level have been found. The aim of this work is to elucidate the function of specific ionotropic glutamate receptors in NG2 glia in the hippocampus of a mouse model of schizophrenia. For this purpose, a mouse model of schizophrenia was generated and validated using immunohistochemistry and behavioural testing. Mice with NG2 glia labelled by a fluorescent protein with a calcium indicator also in NG2 glia were used to observe the activity of glutamate channels and the properties of the extracellular space in these mice. Changes were found in the schizophrenic animals when compared to control animals in the numbers of hippocampal oligodendrocyte lineage cells, in prepulse inhibition and in both volume fraction and tortuosity of the extracellular space in hippocampus. Moreover, the percentage of cells responding to glutamate receptor agonists in NG2 glia in hippocampus also differed significantly between the schizophrenic and the control animals. In conclusion, it can be said that we were able to observe significant changes in the mouse model of schizophrenia that we generated in comparison to control...
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Functional-imaging and electrophysiological correlates of obsessive-compulsive disorder and their potential use in neurofeedback intervention
Kopřivová, Jana ; Horáček, Jiří (advisor) ; Papežová, Hana (referee) ; Stuchlík, Aleš (referee)
Background: Obsessive-compulsive disorder (OCD) is a common mental disorder that may seriously affect quality of life and even the ability to work. Despite advanced medical care there are still patients who do not respond or do not respond sufficiently to treatment. Recently proposed treatment strategies such as deep brain stimulation or repetitive transcranial magnetic stimulation have targeted several levels of fronto-striatal circuits which dysfunction underlies OCD pathophysiology. Likewise, neurofeedback (NFB) could target dysfunctional fronto-striatal networks by providing almost real- time feedback about their activity. As the success of these methods critically depends on good knowledge of dysfunctional loops in OCD, a more detailed investigation of neurobiological basis of this disorder is highly needed. Aims: The aim of the first part of this dissertation was to provide an overview of the current literature related to OCD and NFB. The second section of the thesis is based on five original studies of the author that were conceived to 1) explore anatomical correlate of OCD in our patients, 2) to verify its functional relevance and specificity in electroencephalographic (EEG) studies, and 3) to test the utility of the findings in NFB treatment of OCD. Methods: In our studies we included...
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Physiological and pharmacological aspects of tryptophan and serotonin homeostasis in the fetoplacental unit
Karahoda, Rona ; Štaud, František (advisor) ; Stuchlík, Aleš (referee) ; Kacerovská Musilová, Ivana (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate Mgr. Rona Karahoda Supervisor Prof. PharmDr. Frantisek Staud, Ph.D. Title of Doctoral Thesis Physiological and pharmacological aspects of tryptophan and serotonin homeostasis in the fetoplacental unit The placenta is an ephemeral organ inevitable for the successful course of pregnancy. As the main link between the mother and the fetus, the placenta fulfills numerous roles during gestation, including endocrine, transport, and immunoprotective processes. Proper functioning of the placenta is critical for the normal growth and development of the embryo/fetus. Importantly, the latest research has associated perturbations of maternal conditions (such as pharmacotherapy, malnutrition, diseases, stress, or inflammation) with alterations of the trophoblasts' endocrine, transport, and metabolic functions. Of note is the placental utilization of the essential amino acid tryptophan, suggested as a potential mechanism contributing to fetal programming of adulthood diseases. Tryptophan flux along the serotonin and kynurenine pathways generates metabolites with neuroactive, immunosuppressive, and antioxidant properties. Current literature suggests that fine-tuning of tryptophan metabolite concentrations...
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Hippocampal neuronal representation of a moving object in a novel spatial avoidance task
Ahuja, Nikhil ; Stuchlík, Aleš (advisor) ; Jiruška, Přemysl (referee) ; Telenský, Petr (referee)
In real world environments, animals need to organize their behavior relative to other moving animals or objects; when hunting a predator, when migrating in groups or during various social interactions. In all of these situations, the animal needs to orient relative to another moving animal/object. To understand the role of the hippocampus in this ability we adopted a two-step approach. We developed a task that would mimic important elements of this behavior in the laboratory. The task required the rats to assess not only their distance from the moving object but also their position relative to the object. We further studied how neurons in the hippocampal CA1 subfield encode the subject, the moving object and the environment in the behavioral paradigm and how do these representations interact among themselves. In rats, we aimed to characterize spatial behaviors relative to moving objects and to explore the cognitive mechanisms controlling these behaviors. Three groups of animals were trained to avoid a mild foot-shock delivered in one of three positions: either in front, on the left side, or the right side of a moving robot. Using different variations of the task, we also probed whether avoidance was simply due to increased noise level or size of the retinal image or appearance of the robot. As the...
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Physiology of Blood Brain Barrier
Kellner, Patrik ; Otáhal, Jakub (advisor) ; Stuchlík, Aleš (referee)
This thesis takes on the theme of blood-brain barrier. Blood-brain barrier is a physiological barrier, that divides the circulatory system from brain, in place of their confrontation. Barriers main task is to maintain homeostasis and regulate the transport of substancesin bothdirections.The mostimportant groupof proteins,responsible fortransport, are the ABC transporters. Alterations of barrier properties during the pathological states, but also the distribution of medical drugsis subjectof futherinvestigations.Overview of the above mentionedthemeswillbe mediatedbythis thesis. Key words: Blood-brainbarrier, endothelialcells,tight junctions
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