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Stereological quantification of striatal NPY-positive interneurons and their genetic modification by the AAV5 viral vector
Smolík, Matyáš ; Janíčková, Helena (advisor) ; Chvojková, Markéta (referee)
Different types of interneurons in the striatum are still relatively poorly understood, especially compared to other parts of the brain such as the cortex or hippocampus. One of the lesser-known types of striatal interneurons that has received increasing attention recently, are neuropeptide Y-expressing interneurons (NPY+ interneurons). Available work indicates that these interneurons are controlled by striatal cholinergic interneurons and thus they may serve as mediators of cholinergic modulation in the striatum. The first aim of this thesis is to determine the absolute number of NPY+ interneurons in the mouse dorsal striatum by stereology, using a transgenic mouse model that shows GFP expression in NPY+ neurons. The second aim of this thesis is to use stereology to determine the volume of the dorsal striatum that we are able to target with viral expression when using a standard stereotactic injection protocol commonly used in our laboratory. The third aim of this study is to test the behavioural effect of knock down of the beta2 subunit of the nicotinic acetylcholine receptor expressed by NPY+ interneurons in the dorsal striatum. The work should serve as a first step in a study that will ultimately allow us to develop a quantitative idea of the absolute and relative number of NPY+ interneurons in...
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Special education diagnostic of school readiness
Chvojková, Markéta ; Felcmanová, Lenka (advisor) ; Laurenčíková, Klára (referee)
Special education diagnostic of school readiness Abstract This thesis on Special educational diagnostics of school readiness deals with preparedness of a child entering primary school. It concerns the main features of readiness for school attendance such as physical, perceptual, cognitive and social, emotional and motivational readiness. The first section describes the abilities a pre-school child should posses in terms of aspects mentioned earlier. Subsequently, an emphasis will be given to the enrolment in primary school and then it is followed by the description of legislation and functions of the preparatory classes for primary education. The aim of my thesis paper is to demonstrate the importance of the preparation for systematic graphomotorical skills of children with deferred school attendance who attend preparatory year of elementary school. The theoretical part focuses on diagnosis of auditory and visual perception and graphomotorical skills in a selected group of children (research and control). One element of the paper is dedicated to design an intervention plan for the group of researchers and its subsequent evaluation in the form of re-diagnosis. Keywords School readiness, special education diagnostic
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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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Effects of Neurotransmission-Modulating Multipotent Compounds in Pharmacological Animal Models of Cognitive Deficit
Chvojková, Markéta ; Valeš, Karel (advisor) ; Kuchař, Martin (referee) ; Rudá, Jana (referee)
In preclinical research on Alzheimer's disease pharmacotherapy, attention is paid to multipotent compounds, enabling intensification of the effect by targeting multiple pathophysiological mechanisms. The aim of the thesis was to assess the effect of multipotent compounds and combination therapy in models of cognitive deficit in the rat. The mechanism of action of the tested compounds was modulation of neurotransmitter systems. The aim of the first part of the study was to compare the effect of experimental monotherapy and combination therapy with an N-methyl-D-aspartate (NMDA) receptor antagonist and a γ-aminobutyric acid type A (GABAA) receptor positive modulator in the trimethyltin-induced model. Superiority of the combination therapy was proven by histological analysis of hippocampal neurodegeneration; however, it did not reach statistical significance in the cognitive test. The other part of the thesis focused on multipotent tacrine derivatives. We demonstrated a positive effect of 6- chlorotacrine-6-nitrobenzothiazole hybrid, as well as 6-chlorotacrine-L-tryptophan hybrid, acting as acetylcholinesterase inhibitors, in the scopolamine-induced model of cognitive deficit. Besides, we demonstrated a low risk of serious side effects of other tacrine derivatives acting as NMDA receptor antagonists....
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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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Special education diagnostic of school readiness
Chvojková, Markéta ; Felcmanová, Lenka (advisor) ; Laurenčíková, Klára (referee)
Special education diagnostic of school readiness Abstract This thesis on Special educational diagnostics of school readiness deals with preparedness of a child entering primary school. It concerns the main features of readiness for school attendance such as physical, perceptual, cognitive and social, emotional and motivational readiness. The first section describes the abilities a pre-school child should posses in terms of aspects mentioned earlier. Subsequently, an emphasis will be given to the enrolment in primary school and then it is followed by the description of legislation and functions of the preparatory classes for primary education. The aim of my thesis paper is to demonstrate the importance of the preparation for systematic graphomotorical skills of children with deferred school attendance who attend preparatory year of elementary school. The theoretical part focuses on diagnosis of auditory and visual perception and graphomotorical skills in a selected group of children (research and control). One element of the paper is dedicated to design an intervention plan for the group of researchers and its subsequent evaluation in the form of re-diagnosis. Keywords School readiness, special education diagnostic
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The behavioral effects of NMDA receptor antagonists
Chvojková, Markéta ; Valeš, Karel (advisor) ; Horák, Martin (referee)
NMDA (N-methyl-D-aspartate) receptors are glutamate-gated ion channels, which are located in the central nervous system. They permit excitatory neurotransmission and are crucial for synaptic plasticity and other functions, but on the other hand for excitotoxicity. By the administration of NMDA receptor antagonists it would be possible to restrict the consequences of excessive glutamate exposure. However, the use of many of these drugs is made impossible by their serious behavioral side effects. NMDA receptor antagonists can influence cognitive and motor functions in laboratory animals and also in humans, and can cause temporary psychosis. These negative behavioral effects are most pronounced in the case of non-competitive antagonists. Conversely, the behavioral side effects of uncompetitive antagonists, antagonists selective for NMDA receptors containing a NR2B subunit or NMDA receptor glycine binding site antagonists are milder. From a clinical point of view, some other behavioral effects of NMDA receptor antagonists are beneficial. These effects include anxiolytic and antidepressant effects and also an alleviation of cognitive deficit and behavioral aberration in Alzheimer's disease through the administration of memantine. The aim of this thesis is to summarize the main behavioral effects known to us of...
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