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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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The influence of the neuroactive steroids inhibiting NMDA receptors on behaviour
Chvojková, Markéta ; Valeš, Karel (advisor) ; Mareš, Pavel (referee)
The neuroactive steroid pregnanolone glutamate (Pg glu), a synthetic analogue of the naturally occurring pregnanolone sulfate (3alpha5betaS), has neuroprotective properties and a minimum of adverse effects. The subject of my thesis is the influence of selected structural modifications of the molecule Pg glu on biological effects. The first modification involves an increase of lipophilicity, the second involves the attachment of a positively charged group to C3. All these neuroactive steroids are use-dependent inhibitors of NMDA receptors. The first aim of this thesis was to determine the neuroprotective effectiveness of the neuroactive steroids chosen. The second aim was to explore the influence of selected neuroactive steroids on motor coordination, reflexes, anxiety and locomotor activity, as well as the effect of their high doses. The third aim was to create a battery of behavioural tests for screening the biological effects of analogues of Pg glu in laboratory rodents. The neuroprotective effects were evaluated in a model of excitotoxic damage of hippocampus in the rat on the basis of its behavioural consequences. The neuroprotective efficacy of androstane glutamate (And glu) and Pg glu was demonstrated. In the case of positively charged molecules, neuroprotective efficacy was not demonstrated....
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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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The electroencephalographic changes in animal serotonergic model of psychosis-the study of EEG connectivity in relation to behavior
Tylš, Filip ; Páleníček, Tomáš (advisor) ; Mareš, Pavel (referee) ; Chvátal, Alexandr (referee)
The present thesis deals with the electrophysiological and behavioral correlates of the effects of serotonergic psychedelics in an animal model of psychosis. In the general part, we describe the phenomenology and neurobiology of psychotic diseases and the altered states of consciousness induced by serotonergic psychedelics. Furthermore, we outline the pharmacological models of acute psychosis with a focus on serotonergic substances, particularly the active substances from hallucinogenic mushroom - the indolamine psilocybin and its active metabolite psilocin. We briefly explain the method of quantitative electroencephalography (QEEG) and summarize the main findings of QEEG in animals and humans intoxicated by serotonergic psychedelics. The experimental part of the thesis describes the pharmacokinetics of psilocin, its effects on the behavioral pattern, locomotion and sensorimotor processing of information, as well as sex differences in the behavioral response. A medium dose of psilocin caused atypical behavioral figures, decreased locomotion and disturbance in sensorimotor processing of information, with the females being more resistant to this effect. Another focus of the thesis is the dynamics of QEEG changes in time (EEG absolute power spectra and EEG coherences), as recorded from the cortex of...
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Impact of different types of antidiabetic interventions on the development of neurodegenerative changes in brains of diabetic mice and rats
Popelová, Andrea ; Maletínská, Lenka (advisor) ; Mareš, Pavel (referee) ; Hölscher, Christian (referee)
Alzheimer's disease (AD) is neurological disorder characterized by extracellular beta amyloid plaques and intracellular neurofibrillary tangles formed by hyper-phosphorylated Tau protein. Since type 2 diabetes mellitus (T2DM) is a risk factor of AD development, in the first part of the thesis, a potential relationship between hyper-phosphorylation of Tau protein and central insulin resistance was followed in hippocampi of two models of obesity-induced pre-diabetes, fa/fa rats, and mice with monosodium glutamate (MSG) induced obesity. In both 8-month-old fa/fa rats and 6-month- old MSG mice a decreased phosphorylation of insulin signaling cascade resulted in an increased activation of main Tau kinase glycogen-synthase kinase-3Beta (GSK-3β) and an increased Tau phosphorylation at epitopes Ser396 and Thr231. This phenomenon was less developed in 2-month-old animals. The second part of the thesis was focused on a potential neuroprotective anorexigenic neuropeptide, prolactin-releasing peptide (PrRP), designed at our Institute. Palmitoylation enabled PrRP to cross the blood-brain barrier and employ its central anorexigenic activity. In the third part of the thesis, an effect of 14-day-long SC administration of liraglutide, the most used anti-T2DM drug with central anorexigenic effect, and palmitoylated...
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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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Motor development after repeated dosing of AMPA receptors antagonist in laboratory rats
Hanzalová, Jitka ; Mareš, Pavel (advisor) ; Valeš, Karel (referee)
Substance IEM 1460 is an antagonist of AMPA receptors in the brain. It is a derivative of adamantine, which has already been tested in several studies as a potential age-related anticonvulsant. In the research part of the thesis there is a summary of the knowledge about receptors, focusing on AMPA receptors, IEM 1460, epilepsy and ontogenetic development of laboratory rat. The research section evaluates the effect of IEM 1460 on motor skills of a rat in a few postnatal days of its life. To evaluate spontaneous animal motor skills, Open-Field tracking was used, and several specific tests were used to evaluate provoked motor skills. A total of 30 animals were included in the research. Substances (IEM 1460 at 3 mg / kg, IEM 1460 at 10 mg / kg or 2 ml / kg saline) were infused intraperitoneally on five consecutive days (ages P7-P11) and the animals were repeatedly tested at age 12, 15, 18, 21, 25, 31 and 60 days. In this study, IEM 1460 has not been shown to have significant effect on the gross rat motor skills and therefore the substance remains as a serious candidate for age-specific antiepileptic drugs.
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