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Beneficial Effects of 11β-HSD1 Inhibition on Cognitive Performance in a Mouse Model of Alzheimer's Disease
Červinková, Tereza ; Červený, Lukáš (advisor) ; Musílek, Kamil (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Tereza Červinková Supervisor: PharmDr. Lukáš Červený, Ph.D. Title: Beneficial Effects of 11β-HSD1 Inhibition on Cognitive Performance in a Mouse Model of Alzheimer's Disease The increased life expectancy goes hand in hand with ageing-related cognitive impairments. Alzheimer's disease (AD) is the most common type of dementia being an irreversible and progressive brain disorder with loss of cognitive functions. Recent studies suggest that excess of glucocorticoid (GC) action exerts deleterious effects on the hippocampus and causes impaired spatialmemory. In addition, it has been demonstrated that aged mice with cognitive deficits show increased gene expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the hippocampus and parietal cortex. The Senescence-Accelerated Mouse Prone 8 (SAMP8) strain is a spontaneous animal model of accelerated ageing. Many studies indicate that SAMP8 harbour the behavioural and histopathological signatures of AD. In the present study, we evaluated the neuroprotective effects of 11β-HSD1 inhibition by a potent pyrrolidine-based compound RL-118 and/or effects of diet on cognitive performance in different groups of SAMP8 by conducting behavioural and...
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Changes in Hormone Levels in Female Basketball Players and Their Relationship with Emotional state and Efficiency
Zikánová, Tereza ; Pivoňková, Věra (advisor) ; Hroníková, Linda (referee)
This thesis focuses on women's competition in female basketball players and their hormonal responses to winning and losing. We tested saliva samples of 29 female players for testosterone and cortisol which were collected in three phases: baseline samples, pregame samples and after game samples. In every collection phase we also inquired about the emotional state of mind of the respondents. Players completed a survey examining their subjective evaluation of the match result. We also used statistical data from every match, which provided an objective evidence on the players' usefulness. All the aforementioned variables were examined in relation to the testosterone and cortisol levels. The results have revealed that the cortisol levels are responsive to the match results, whereas the losing players display a significant rise of the stress hormone level after the match. The winners display only a slight increase in the cortisol levels. Testosterone levels did not prove to react to the match results. However, it was discovered that the winners exhibited higher levels of testosterone in all collection phases than their competitors. Nevertheless, the difference between the winners and the losers was not significant in any of the cases. The winners felt more positive after the match than the losers. The correlation...
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Pineal lesions: clinical presentation, hormone secretion, sleep quality and effect of surgical treatment
Májovský, Martin ; Netuka, David (advisor) ; Šonka, Karel (referee) ; Lipina, Radim (referee)
Introduction: Pineal region is a deep-seated part of the brain surrounded by highly eloquent structures. Differential diagnosis of space-occupying lesions in this region encompasses pineal gland cysts, pineal gland tumours, metastases, germ cell tumours, meningiomas, gliomas, hemangioblastomas and neuroectodermal tumours. In this thesis, I focused mainly on patients with pineal cysts, which is a benign affection of the human pineal gland on the borderline between pathology and normality. The clinical management of patients with a pineal cyst remains controversial, especially when patients present with non-specific symptoms. A melatonin secretion in patients with a pineal cyst before and after a pineal cyst resection has not been studied yet and the effect of surgery on human metabolism is unknown. Materials and Methods: We performed a prospective study between 2000 and 2016. All patients with a pineal cyst larger than 7 mm were included. Epidemiological data, presenting symptoms, surgical results and radiographic and clinical follow-up were documented. We examined melatonin, cortisol and blood glucose secretion profiles perioperatively in a subgroup of 4 patients. The control group was represented by 3 asymptomatic patients with a pineal cyst. For each patient, 24-h circadian secretion curves of...
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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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Neuroimmune and endocrine correlates of stress response and dissociation in affective disorders
Bízik, Gustáv ; Bob, Petr (advisor) ; Horáček, Jiří (referee) ; Yamamotová, Anna (referee)
Depression and other mental disorders are the leading cause of disability worldwide and their burden has increased considerably over past decades. However, advances in psychopharmacology of psychiatric disorders are not in measure with this negativ trend. As a result, a large body of researchinpsychiatryandneurosciencestries to furtherourunderstanding of pathophysiologicalmechanismsunderlyingmooddisorders andothermentalillnesses in order to improve the efficacy of current treatments and to identify new therapeutic agents. According to current evidence, stress-related pathways and inflammation processes are directly involved in thedevelopment of depressive disorder andseveral other psychiatric conditions.Thestudy of the effects and consequences of stress exposure requires an interdisciplinary approach,taking into account specific aspects of the "inputs", such as chronic stress and traumatic experiences, and related psychological processes, with the crucial role of dissociation. Following these theoretical findings, the empirical research performed in two cohorts of inpatients with depressive disorder focused on immune and endocrine responses to stress and their relationship to psychopathological symptoms, specifically trauma-related symptoms, psychic and somatoform dissociation and depressive...
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The stress response to cardiac catheterisation. The concentration of stress markers of the hypothalamic-pituitary-adrenal axis
Skarlandtová, Hana ; Kittnar, Otomar (advisor) ; Gregor, Pavel (referee) ; Svoboda, Miroslav (referee)
In our study, we analyzed four stress markers (cortisol, cortisone, DHEA and DHEAS) in blood serum in young sows using minimally invasive heart catheterisation as the stress factor. The marker levels were assessed in four defined periods of the experiment, beginning with the baseline level on the day before intervention (1), the second period was after the introduction of anaesthesia (2), the third was after conducting tissue stimulation or ablation (3), and the final period was after the end of the catheterisation (4). Cortisol and cortisone were detected using HPLC method, DHEA(S) by commercial kits. For statistical analyses non-parametric tests were used (due to non standard Gaussian data distribution). In our study we arranged these experiments: 1. Diurnal variability in these markers concentration during heart catheterisation was tested. 2. Are there differences between stress markers concentration the day before experiment (sampling 1) and in the day of the catheterisation (samplings 2, 3, 4)? 3. Are there differences between these markers concentration during operation (the first sampling was excluded)? 4. The cortisol/cortisone ratio was calculated. We found only minimal statistical differences in studied markers between the morning and afternoon group (p > 0.05) in experiment 1. For tested...
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Physiologic and pathophysiologic aspects of selected endocrinopathies. Their relationship to adipose tissue matebolism and insulin resistance
Ďurovcová, Viktória ; Kršek, Michal (advisor) ; Saudek, František (referee) ; Štich, Vladimír (referee)
The pathogenesis of insulin resistance is a complex and still intensively studied issue. Endocrine and paracrine activity of the adipose tissue together with mi- tochondrial dysfunction are the most discussed potential factors included in the development of insulin resistance. In the first part of our study we examined the involvement of the adipose tissue and its secretory products in the etiopathogenesis of insulin resistance in patients with Cushing's syndrome, acromegaly and simple obesity. We focused on three important regulators of metabolic homeostasis - fibroblast growth factors 21 and 19 (FGF-21 and FGF-19) and adipocyte fatty acid binding protein (FABP-4). We found significantly elevated circulating levels of FGF-21 and FABP-4 ac- companying insulin resistance in both patients with simple obesity and patients with obesity connected to Cushing's syndrome, as compared to healthy controls. The concentrations of both substances were comparable between hypercortisolic and obese patients. This finding together with the absence of correlation be- tween the levels of FGF-21 resp. FABP-4 and cortisol suggest that the reason for elevation of their concentrations is obesity and its metabolic consequences themselves rather then the effect of hypercortisolism on FGF-21 and FABP-4 production. We found no...
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Neuroanatomical aspects of nonGmotor effects of deep brain stimulation
Růžička, Filip ; Růžička, Evžen (advisor) ; Papežová, Hana (referee) ; Druga, Rastislav (referee)
Summery The underlying mechanisms of weight gain and other affective and cognitive changes after initiation of deep brain stimulation in Parkinson's disease are still unclear. Considering the functional organization within the subthalamic nucleus (STN); limbic, associative and sensorimotor regions residing in the medial, central and later STN respectively, we hypothesized that weight gain may be related to medial localization of stimulation, while motor improvement may be related to lateral localization of stimulation within the STN (study 1). We further hypothesized that stimulation close to the limbic and associative part of the STN may be associated with negative impact on limbic system leading to enhanced anxiety and changes in the hypothalamic- pituitary- adrenal axis (HPA)(study 2). Therefore, the primary aims our study were to assess changes in body weight (study 1) and the hypothalamic- pituitary- adrenal axis (HPA) (study 2) in relation to the position of the active stimulating contact within the nucleus. ...
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The role of gut microbiota and HPA axis in childhood
Trunečková, Naděžda ; Kaňková, Šárka (advisor) ; Kreisinger, Jakub (referee)
The microbiota-host relationship is a complex system of interactions, which has evolved over thousands of years. Colonization of the gastrointestinal tract begins in prenatal period, continues after birth, and can be disrupted by different factors like a mode of delivery, lactation, or antibiotics. Main development of the intestinal microbiota and the central nervous system takes place in the first two or three years of life. The microbiota and the brain can mutually influence their development. For the communication is used the microbiota-gut-brain axis, which includes the neural, endocrine, metabolic and immunological pathways. Exposure to stress, whether in the prenatal period or in the first few years of life, can have a negative impact on the composition of the intestinal microbiota and the developing brain, including areas associated with the regulation of the HPA axis - one of the main mechanisms of stress regulation, which includes all interactions between the hypothalamus, pituitary gland and adrenal glands. Dysregulation of the microbiota-gut-brain axis can affect our response to stress, cognitive function, and emotions. The modified HPA axis response can affect our physical and mental health. It is associated with immune system disorders, behavioural disorders, social integration...
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