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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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G peoteins and adenylyl cyclase during onhogenetic development of rat brain cortex
Stohr, Jiří ; Svoboda, Petr (advisor) ; Langmeier, Miloš (referee) ; Mareš, Pavel (referee)
CONCLUSIONS our measurementsof agonist.stimulatedhigh-affiniý GTPase activiý and GTftS binding in thedevelopingrat brain cortexhaverevealeda markedlyhigherfunctionalactivity of GTP.binďng proteins in adult (9O{ay.old) than in immaturate(12day.o1d) ťaB.This study further demonsbatesthat RGSI, by contrast to RGSI6, might function as srong regulatorofhigh-afiiniý GTPase activity in this tissue. AC activity is regulatedsimilarly in brain cortex from immaturateand adult rats,but theenzymeactivity is much lower in adultthanin immaturateanimals.As arguedpreviously, the ďfference betweenAc actiúty in thesetwo agegroups is not explicable on the basis of the dwelopmental expressionprofiles of either ACl, ACz, AC4 and AC6 or ďfferent G proteins(Ihnatorrychet a1.,2@2a;Ihnatov.vchetal.,2002b).Itmightbe speculated,however, that the complement of some other types of AC could gg slanged in adulthood. This supposition is supportedby our recent finding of altered characteristicsof [3H]forskolin binding in cerebrocorticalmembranesfrom adult comparedto imÍraturaterats (Stóhr et al., 2005b)-Nevertheless,a possibilitycan not be ruled out thatAC activityin adultrat brain cortex might be perhaps affected by some yet not known negative regulatory factor/mechanism,which is switchedon shortlyaftermaturation. That high-afÍiniý as well...
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Effect MTEP on immature rat behaviour.
Tichá, Kateřina ; Mareš, Pavel (advisor) ; Telenský, Petr (referee)
Metabotropic glutamate receptors represent prospective targets for anticonvulsant therapy of epilepsy. However there may be serious negative side effects. In this study the highly specific antagonist of mGluR5 was used - MTEP, [(2-methyl-1,3-thiazol-4-yl)ethynyl] pyridine, which was shown previously to have an anticonvulsant action. Our study was aimed at other possible effects, such as efficacy in motor skills, spontaneous behaviour, space learning and rate of anxiety. Animals, immature male Wistar rats (12, 18 and 25 days old), were pretreated with MTEP in two different doses - 20mg/kg and 40mg/kg, because MTEP demonstrated anticonvulsant activity in exactly such high doses. Animals were tested 15 min, 60 min and 24h (in elevated plus maze test only) after treatement. No negative effects were found in motor tests;, space learning in elevated plus maze was also not compromised. On the other hand, MTEP influenced frequency of some types of stereotypic behaviour in the open field test. MTEP exhibited anxiolytic-like effect in elevated plus maze in immature rats; this side effect has to be taken as a positive one. Powered by TCPDF (www.tcpdf.org)
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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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