|
| |
|
| |
|
|
The interaction of kainate subtypes of glutamate receptors with steroid compounds.
Fraňková, Denisa ; Krůšek, Jan (advisor) ; Adámek, Pavel (referee)
Kainate receptors belong to the family of glutamate receptors, which include NMDA, AMPA and δ receptors. Glutamate receptors are widely found in the brain and therefore they are very dynamically investigated, especially from view of pharmacology, because there is great potential for finding new and more specific modulators which could be used in the treatment of neurodegenerative diseases. The aim of this work was to extend the knowledge about the influence of neurosteroids on homomeric kainate receptors (GluK1, GluK2, GluK3) in which is the study of modulation by neurosteroids still at the beginning. We have investigated interactions of homomeric kainate receptors with selected neurosteroids (pregnenolone sulfate, pregnanolone sulfate, dehydroepiandrosterone, dehydroepiandrosterone sulfate) by using patch clamp method in the configuration of whole-cell recording and also by using microfluorometry. We have found out that the biggest modulating effect on homomeric kainate receptors is caused by pregnenolone sulfate, which inhibits glutamate responses of these receptors. Keywords kainate receptor, glutamate, neurosteroids, steroids, patch-clamp technique
|
|
|
The role of neuroactive steroids in pregnancy and their importance in prenatal diagnosticsSteroidogenesis in the third trimester of pregnancy and mechanisms leading to the start of labor
Pašková, Andrea ; Pařízek, Antonín (advisor) ; Procházka, Martin (referee) ; Tošner, Jindřich (referee)
Steroid hormones act through two mechanisms. The first is the classical genomic level, which acts at a relatively slow pace from hours to days. The second non-genomic mechanism of steroid activity can influence cellular function during seconds or even milliseconds. During pregnancy both mechanisms take place. Steroid hormones that act non-genomically and influence neuronal excitability are called neuroactive steroids. The aim of this study was to measure the levels of steroid hormones and examine their relationship to the physiology and pathophysiology of pregnancy. The physiological importance of increased placental progesterone production, lowered production of 5B-pregnanone steroids and increased activity of steroid sulfotransferase with gestational age have been intensely discussed. On the basis of our results, we have proposed an alternative mechanism of maternal progesterone synthesis during pregnancy (progesterone, or the gestagen stabilizing activity of the myometrium = continuation of pregnancy). In contrast to previous results our observations indicate that gestagens arise from precursors in the fetus (from pregnenolone sulfate). This mechanism is closely connected with the distribution of placental oxido-reductase. Data from this study show an increasing trend in the conversion of...
|
|
|
Neuroactive steroids in human physiology and pathophysiology
Kubátová, Jana ; Hill, Martin (advisor) ; Fanta, Michal (referee)
The present diploma thesis is focused on the evaluation of steroid metabolome in body fluids in human pregnancy and parturition and also concentrates on the estimation of steroids in men with epilepsy (MWE) regarding the influence of epilepsy and its treatment with antiepileptic drugs (AEDs). The results obtained eventuate to the following conclusions: 1. They support the proposition about the key importance of corticoliberin for the timing of human parturition via stimulation of the steroidogenesis in the fetal zone of the fetal adrenal (FZ). Changes in steroid levels, however, much better predict the timing of parturition than the variation in corticoliberin. 2. The distribution of isoforms of placental oxidoreductases determines the excess of oxidized forms of the sex steroids and NAS in the fetus and the excess of their reduced forms in mother. This mechanism fundamentally affects the steroid bioactivity. The results indicate the role of NAS in pregnancy sustaining, their analgesic effect around parturition and their role in the pathophysiology of postpartum blues.
|
|
| |
|
| |
|
| |
|
| |
|
| |
guest ::
