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Physiological and neurobiological correlates of personality traits
Kubelková, Klára ; Nekovářová, Tereza (advisor) ; Jonáš, Juraj (referee)
This paper seeks to provide an overview of the molecular, genetic, as well as structural and functional correlates of personality traits known to date, focusing primarily on typology according to the extensively used "NEO PI-R" ("Big Five") classification. It also attempts to discuss, at least briefly, the methodology for obtaining both neurobiological and psychological data and its validity. Finally, it aims to highlight the strengths and weaknesses of the neurobiological approach to personality, its potential benefits and pitfalls. It does not aim to establish the exact proportion of biological and sociological factors, but to elucidate the mechanisms involved in this biological conditioning. Although there is now a vast amount of research on the biological substrate of personality, there is considerable inconsistency among these studies, both in terms of methodology and the results provided. Moreover, only a small number of them attempt to explain their findings in terms of possible mechanisms of their effect and thus to integrate them into the broader picture of the brain-personality connection. These and many other limitations of neurobiological research on personality, which receive considerable attention in this thesis, are only a proof of the immense complexity of the human brain and human...
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Role of the serotonin receptor type 7 (5-HT7) in autoimmune disease
NUßBAUMER, Mia
Serotonin receptor type 7 (5-HT7) displays immunomodulatory functions and is overexpressed in individuals with Crohn's disease. Here, we set out to determine 5-HT7 mode of interaction with its cognate proteins Gs and G12. A unique type of coupling, termed 'inverse coupling' is known to occur between the 5-HT7 receptor and the Gs protein. The aim of our research was to determine whether G12 can also undergo this kind of coupling. We found that the G12 protein has a surprisingly lower mobility than Gs implying a specific interaction with a membrane domain or another membrane-localized protein. For both G proteins, we were unable to detect their inverse coupling with the 5-HT7 receptor at room temperature. Our findings indicate peculiar differences in G protein mobility and emphasize the importance of temperature for studies of interactions between G proteins and G protein-coupled receptors.
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Effect of antidepressants on placental monoamine homeostasis
Horáčková, Hana ; Štaud, František (advisor) ; Sumová, Alena (referee) ; Soukup, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Kralove Department of Pharmacology and Toxicology Candidate: Mgr. Hana Horackova Supervisor: prof. PharmDr. Frantisek Staud, Ph.D. Title of doctoral thesis: Effect of antidepressants on placental monoamine homeostasis Depression in pregnancy is an increasingly common problem and it is reported that up to 25 % of pregnant women suffer from depression and approximately 13 % are prescribed antidepressants. Currently, the most commonly prescribed antidepressants in pregnancy are selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). However, the safety of these treatments is still controversial, as poor pregnancy outcomes such as organ malformations, increased incidence of neurological disorders, and preeclampsia have been reported in pregnant women taking antidepressants. However, knowledge of the responsible mechanisms is still lacking at present as they have not been sufficiently investigated. Although the effect of antidepressants on the availability of serotonin (5-HT), dopamine (DA) and norepinephrine in brain tissue has been extensively characterized in the literature, the interactions of antidepressants with placental monoamine transporters have not received attention to date. However,...
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The influence of antidepressants on serotonin homeostasis in placenta
Váchalová, Veronika ; Štaud, František (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Veronika Váchalová Supervisor: Prof. PharmDr. František Štaud, Ph.D. Consultant: Mgr. Rona Karahoda Title of diploma thesis: The influence of antidepressants on serotonin homeostasis in placenta Depression is a serious mental disorder affecting 10-20% of women during pregnancy. Up to 10% of these pregnant women are prescribed antidepressants (ADs), most frequently from the class of selective serotonin (5-HT) reuptake inhibitors (SSRIs). While the safety of this treatment is questionable due to reported impaired pregnancy/fetal outcomes, understanding of potential mechanistic causes is still lacking. During pregnancy, 5-HT is important for normal placental function and proper fetal development and programming. 5-HT homeostasis in the placenta is maintained via the 5-HT transporter (SERT/SLC6A4) on the apical side and the recently characterized organic cation transporter 3 (OCT3/SLC22A3) on the basal side of trophoblast. These transporters take up 5-HT from the maternal and fetal circulations, respectively into the syncytiotrophoblast (STB) where it is degraded by monoamine oxidase-A (MAO-A). As all ADs interfere with the 5-HT system it is important to study their potential interactions in the...
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Effect of cholinesterase inhibitors on monoaminergic system and energic metabolism
Kalinová, Tereza ; Mladěnka, Přemysl (advisor) ; Štěpánková, Šárka (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Tereza Kalinová Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Mentor: Assoc. Prof. Jana Hroudová, Pharm.D., Ph.D. Title of diploma thesis: Effect of cholinesterase inhibitors on monoaminergic system and energy metabolism Cholinesterase (ChE) inhibitors play an essential role in the treatment of Alzheimer's disease (AD). They effect positively cognitive, functional and behavior symptoms of AD. Up to date, donepezil, rivastigmine and galantamine represent the only ChE inhibitors approved for AD treatment. The first ChE inhibitor was tacrine, which was withdrawn from market due to its toxicity and adverse effects. Recently, novel tacrine and 7-methoxytacrine (7-MEOTA) derivatives were synthetized and extensively investigated to find less toxic compounds affecting pathological mechanisms associated with development of AD. There is less known about effects of these drugs on mitochondrial functions and cellular energy metabolism. The aim of this project is to examine in vitro effects of ChE inhibitors on energy metabolism and cellular respiration, specifically on mitochondrial electron transport chain complexes and an enzyme of the citric acid cycle - citrate synthase. Inhibitory effects...
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The influence of central serotoninergic and dopaminergic activity on nutritional and metabolic parameters
Brunerová, Ludmila ; Anděl, Michal (advisor) ; Haluzík, Martin (referee) ; Yamamotová, Anna (referee)
THE INFLUENCE OF CENTRAL SEROTONINERGIC AND DOPAMINERGIC ACTIVITY ON NUTRITIONAL AND METABOLIC PARAMETERS MUDr. Ludmila Brunerová SUMMARY Introduction: Neuromediators dopamine and serotonin play a significant role in homeostatic and hedonic regulation of food intake, may exert direct metabolic effects and particularly serotonin influences affectivity. Their central activity could be quantified by functional tests. Common regulatory mediators of metabolism and affectivity represent an interesting research goal. Aims of study: The first aim was to describe the relationship between central serotoninergic activity measured by citalopram challenge test, affectivity, preference of macronutrients in food and metabolic profile in healthy men. The second aim was to confirm the use of sublingual apomorphine test as a functional test for assessment of central dopaminergic activity. The third aim was to reveal the relationship between central dopaminergic activity measured by sublingual apomorphine test, preference of macronutrients and metabolic profile. Methods: The study was performed on 42 healthy men (average age 43.5 ± 7.4 years and average BMI 27.4 ± 5.7 kg/mš) within 4 days with a week interval in between them. Anthropometric and...
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Determination of tryptophan, serotonine and melatonin in plants by using HPLC
Pavlů, Věra ; Křížek, Tomáš (advisor) ; Kozlík, Petr (referee)
This thesis deals with the development and optimization of a method for the determination of tryptophan and its metabolites - serotonin and melatonin - in plant material, in grapevine, during one analysis. It uses a high-pressure liquid chromatography. The theoretical part is about tryptophan, its metabolism and basic properties of its metabolites - serotonin and melatonin. Their occurrence in wine is also discussed. Analytical techniques by which these analytes can be determined are also provided. Then information about modern stationary phases, that are suitable for this species, is included. The experimental part consists of optimization of the method, measurement of calibration dependences and measurement of real samples. It is measured by the method of reverse phase chromatography. As first stationary phase it is used a C18 column with core-shell packing, second is a BEH Phenyl column. The mixture of 10 mM acetate buffer (pH = 4.5) and methanol is used as the mobile phase. For detection UV at wavelength 254 nm is used, then for greater sensitivity mass detectionis is used. The basic conditions for the experiment have been set. At the beginning of the analysis, the mobile phase contains 95 % (v/v) buffer and 5 % (v/v) methanol. Then the methanol content is linearly increased to 80 % (v/v) from...
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Study of surface modifications of boron doped diamond electrode for voltammetric detection of dopamine and serotonin
Eremina, Anna ; Schwarzová, Karolina (advisor) ; Dejmková, Hana (referee)
This diploma thesis deals withthe studyof electrochemical behaviorand detection of two structurally different neurotransmitters, dopamine (DA) and serotonin (5-HT), in solutions commonly used for neuron cultivation, namely Neurobasal (NB), NB with phenol red and in phosphate buffer (PB) of a pH close to the physiological value. An electrode based on boron-doped diamondwas used for the study, examiningtwo types of surfaces obtained after oxidation (O-BDD) and mechanical polishing (p-BDD). The results were obtained by two voltametric techniques,namely cyclic and differential pulse voltammetry.The studyrevealedthat DA oxidationis a quasi-reversible process,whereas 5-HT oxidizes irreversibly on O-BDD and p-BDD. Nevertheless, for both neurotransmitters their anodic oxidationonboth BDD surfaces is controlledby diffusion. Due to the passivation of the electrode surface by the oxidation products, anodic reactivation(Eact = +2400 mV, t = 30 s) was first testedto regenerate the O-BDD surface during DA and 5-HT measurements. There was no continuous decrease in DA peak currents on O-BDD and the measuredsignals were characterizedby high repeatabilityin all studiedmedia (sr (Ip) 1.1% in PB of pH 7.0, 1.7% in NB of pH 7.34, 0.9% in NB with phenol red of pH 7.48). In the case of 5-HT, the anodic reactivation was...
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Modification of boron doped diamond electrode by poly-L-lysine and its influence on electrochemical behaviour of dopamine and serotonin
Pejzlová, Michaela ; Fischer, Jan (advisor) ; Vyskočil, Vlastimil (referee)
This bachelor's thesis deals with the redox behavior of two neurotransmitters, dopamine and serotonin, at bare anodically activated (O-terminated) and poly-L-lysine-coated boron doped diamond electrode in two media, namely phosphate buffered saline and Neurobasal (medium commonly used for neuron cultivation experiments). Oxidation of dopamine in tested environments has a quasi-reversible character, while serotonin oxidizes irreversibly on boron doped diamond electrode, both O-terminated and poly-L-lysine-treated. Clearly, poly-L-lysine modification of boron doped diamond electrode leads to a decrease in peak currents and a positive shift in oxidation potentials compared to the O-terminated boron doped diamond electrode; interestingly, serotonin is much more sensitive to polymer coating than dopamine, particularly in Neurobasal medium. During successive measurements, a considerable decrease in recorded signals of both neurotransmitters can be observed. Hence, possibilities how to ensure stable current values were investigated: for dopamine, stirring the solution between the individual scans is sufficient method for obtaining repeatable signals (sr = 1.4-11.9 %, n = 5). However, in case of serotonin it is necessary to reactivate the electrode surface anodically in H2SO4 (Eact = +2400 mV) for 5...
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