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Effects of allopregnanolon on motor functions of young laboratory rat.
Krejčí, Lukáš ; Mareš, Pavel (advisor) ; Valeš, Karel (referee)
Allopregnanolone is a typical representative of neurosteroids. It can be formed by de novo synthesis directly in the CNS or as a metabolite of progesterone. It is an allosteric modulator of GABAA receptors, due to which it has anxiolytic, sedative and anticonvulsant effects. This work investigates the effect of allopregnanolone (ALLO) on the locomotor skills of laboratory rat pups. The results will serve as a reference study for the work of Tereza Košťálová (2020), who investigated the newly discovered neuroactive steroid pregnanolone pyroglutamate (PPG). This exogenous steroid, synthesized at the Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic (IOCB PRAGUE), offers potential use in the treatment of epilepsy. Our goal was to perform the same battery of motor tests after the application of allopregnanolone as a comparison, to what extent and in what way these two substances acutely affect the motor performance of the rat pup. The theoretical part of the thesis describes the physiological mechanisms of neurosteroids in the human body and their potential in the treatment of serious diseases, especially epilepsy. Next, the ontogenetic development of the rat's motor skills is described and compared to humans. The methodology describes the selection and...
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The influence of perinatal hypoxia on motoric development on laboratory rat and means of therapy
Vachovcová, Sylva ; Mareš, Pavel (advisor) ; Stuchlík, Aleš (referee)
Severe perinatal hypoxia represents a substantial brain injury in human newborns. This Diploma thesis is focused on long-term motor outcome of laboratory rat after moderate perinatal hypoxia. We described some behavioral test for detection motor development and presented the influence of perinatal hypoxia on central nervous system. We also discussed an effect of agonists and antagonists of adenosine A1 receptor in brain. The aim of an experimental part was an evaluation of long-term motor behavior in rats affected by perinatal hypoxia. To cause perinatal hypoxia we put pregnant female rats to a hypoxic (10% O2) normobaric room in 11th day of their gestation. The pregnant female rats stayed in hypoxic room until they gave a birth and 6 more days after birth with their litters. For classification of motor development we used battery of tests of motor coordination. These tests correspond to the level of development of the rat. Then a group of rats with perinatal hypoxia was treated by a single administration of an agonist of adenosine A1 receptor 2-chloro-N(6)- cyclopentyladenosin (CCPA) in postnatal day 14. The animals affected by perinatal hypoxia show motor deficits in 3 from 4 selected behavioral tests. Otherwise, this motor behavior was no longer detected in young adults. The rats affected by...
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Possible influencing the motor performance of developing rats by repeated administration of the NMDA receptor antagonist specific for NR2 subunit
Kozlová, Lucie ; Mareš, Pavel (advisor) ; Valeš, Karel (referee)
Nonspecific NMDA receptor antagonists induce hyperlocomotion in rats. The aim of this work is to determine whether the NMDA receptor antagonist specific for NR2 subunit exhibit similar negative effect as nonspecific antagonists. This subunit is predominant in the brain in the early postnatal period. The introduction summarizes the data on NMDA receptors and the development of rat. The experimental part deals with the action of a specific NMDA receptor antagonist Ro 25-6981 on motor performance of developing rats. Substance was repeatedly administered to rats at postnatal days 7 to 11. Spontaneous locomotion and motor performance of the animals were repeatedly tested up to adulthood by battery of tests appropriate for individual ages. Our research demonstrated that this substance does not have significant effect on motor system of laboratory rat and that it might be further tested as a possible age-bound antiepileptic drug.
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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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Effects of a neuroactive steroid on motor skills of young laboratory rat.
Košťálová, Tereza ; Mareš, Pavel (advisor) ; Valeš, Karel (referee)
The steroid substances with effect on nervous tissue are plenteously studied in last years. Their biggest benefits are especially anticonvulsant and anxiolytic effects. This thesis inspects the influence of newly discovered neruactive steroid pregnanolone pyroglutamate synthesized in The Institute of Organic Chemistry and Biochemistry of the Czech Academy of Science (IOCB CAS), which offer potential opportunity of a new therapy of epilepsy from actual pharmacokinetic results. Our goal was to detect, if this substance has any negative effects on locomotor skills of young laboratory rats. In theoretical part of the thesis the development of laboratory rat is briefly descibed, especially its motor skills and sensory functions in comparison with human. The process of the experiments and choice of especially motor skill tests are described in Metogology part. The results of experiment and its comparation with the effect of other neuromediators are introduced and discussed in the practical part of this thesis. There were no serious effects of pregnanolonepyroglutamate applied repeatedly in perinatal period on motor performance. Acute administration of the highest dose of PPG to 12-day-old rat pups resulted in prolongation of time in surface righting and negative geotxis tests. This data are positive for...
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Assessment of the impact of phenytoin on motor activity development of laboratory rats by motor activity testing and swimming analysis
Matoušková, Kateřina ; Mareš, Pavel (advisor) ; Valeš, Karel (referee)
Phenytoin is well-known antiepileptic drug with high anticonvulsant effect but also with proven side effects on motor activities associated with its long-term use. This thesis summarizes side effects of phenytoin on motor skills and coordination of rats after acute phenytoin treatment. Theoretical part includes proven effects of phenytoin on human and animal model. Knowledge about motor skills development of rats and comparison with human motor skills development is also included in the thesis. Apart from locomotion development, swimming development is also described. We compared three groups of rats in the experiment. Each group consisted of ten rats. We compared group with dosage 60 mg/kg, 30 mg/kg, control group and vehicle group. Each group was tested before application for control. We tested animals on postnatal day 12, 18 and 25. Effects of phenytoin were evaluated by motor skills testing and swimming analyses. The results of this thesis have proved impaired motor skills and coordination after phenytoin treatment of 12 and 25 days old rats.
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Possible influencing the motor performance of developing rats by repeated administration of the NMDA receptor antagonist specific for NR2 subunit
Kozlová, Lucie ; Mareš, Pavel (advisor) ; Valeš, Karel (referee)
Nonspecific NMDA receptor antagonists induce hyperlocomotion in rats. The aim of this work is to determine whether the NMDA receptor antagonist specific for NR2 subunit exhibit similar negative effect as nonspecific antagonists. This subunit is predominant in the brain in the early postnatal period. The introduction summarizes the data on NMDA receptors and the development of rat. The experimental part deals with the action of a specific NMDA receptor antagonist Ro 25-6981 on motor performance of developing rats. Substance was repeatedly administered to rats at postnatal days 7 to 11. Spontaneous locomotion and motor performance of the animals were repeatedly tested up to adulthood by battery of tests appropriate for individual ages. Our research demonstrated that this substance does not have significant effect on motor system of laboratory rat and that it might be further tested as a possible age-bound antiepileptic drug.
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Study of the metabolism of 17α-ethinylestradiol by cytochromes P450
Valášková, Petra ; Černá, Věra (advisor) ; Levová, Kateřina (referee)
A synthetic estrogen 17α-ethinylestradiol (EE2) is the main active component of the hormonal contraceptive pills. The rise of consumption of hormonal contraceptives has increased the risk of the back negative effects of EE2 to aquatic organisms. EE2 belongs to the endocrine disruptive compounds known for mimicking natural hormones. A more detailed examination of the transformation of this compound in vivo and in vitro can contribute to a better understanding of its negative effects. This master thesis is therefore devoted to the study of the metabolism of EE2 in two selected model organisms. The ligninolytic fungus Pleurotus ostreatus is the type of fungi with promising biodegradation ability to a lot of pollutants. These properties have led to numerous studies of the degradation potential of P. ostreatus towards EE2, with the possibility of removing this compound from the environment. EE2 has been degraded by the fungus P. ostreatus in vivo resulting in one hydroxylated metabolite, which estrogenic activity is in need for further study. In vitro studies were carried out with a microsomal fraction isolated from the mycelium of this fungus. The conversion of EE2 in vitro via CYPs dependent on NADPH has not been demonstrated, however using KHP as a cofactor, there was one metabolite of EE2 found,...
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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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