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Separation of hippocampal function in Morris water maze and in active place avoidance by alternance protocol
Vojtěchová, Iveta ; Petrásek, Tomáš (advisor) ; Hiadlovská, Zuzana (referee)
In this work, we examined the executive functions of the hippocampus at the behavioral level as a so-called behavioral separation in adult rats. We studied an impact of day-to-day alternation versus sequential learning (and the order of learning) of two spatial tasks (Morris Water Maze and Active Allothetic Place Avoidance) testing different hippocampal functions (experiment 1), or an impact of sequential versus alternating learning of one task (Active Allothetic Place Avoidance) in two different rooms (experiment 2), on performance. We found out that rats are able to learn both tasks as well as to discriminate between the two contexts regardless of the order or alternating of learning. Because such executive functions are impaired in human patients suffering from schizophrenia, we used this procedure also in the rat model of schizophrenia induced by acute intraperitoneal application of dizocilpine (MK-801), glutamate NMDA receptors antagonist, in the dose of 0.08 mg/kg. We failed to selectively disrupt the behavioral separation, however, we observed general learning deficit and hyperlocomotion regardless of the alternation in the Active Allothetic Place Avoidance task in these rats. The cognitive impairments in connection with learning after such low dose of MK-801 in this task have not yet been...
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The effect of agonist of the metabotropic glutamate receptors LY 379268 in an animal model of psychosis
Rišňovská, Dominika ; Stuchlík, Aleš (advisor) ; Telenský, Petr (referee)
Introduction: Schizophrenia is a neuropsychiatric illness characterized by impairments in cognition and positive and negative symptoms. As currently used antipsychotics do not treat all symptoms of the disease, further research of the therapeutic potential of various drugs in the treatment of this disease is crucial. Psychosis is a condition or a mental state that usually accompany schizophrenia, as well as other disorders. We used MK-801, a non-competitive antagonist of NMDA receptors to induce an experimental model of psychosis in rats. By binding to the NMDA subtype of glutamate receptors located on inhibitory interneurons, MK-801 has been shown to elicit an overactivation of cortical and hippocampal pyramidal neurons, leading to behaviors such as hyperlocomotion, stereotypy or cognitive impairments. LY 379268, an agonist of group II metabotropic glutamate receptors, binds to both presynaptic and postsynaptic receptors on pyramidal neurons. It has been suggested that it could alleviate the MK-801-induced hyperactivity of the principal neurons. In this study, we sought to demonstrate the effects of LY 379268 in the MK-801 animal model of psychosis and hypothesized that LY 379268 will ameliorate deficits in the reversal learning induced by MK-801. Materials and methods: Long Evans rats received...
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The effect of agonist of the metabotropic glutamate receptors LY 379268 in an animal model of psychosis
Rišňovská, Dominika ; Stuchlík, Aleš (advisor) ; Telenský, Petr (referee)
Introduction: Schizophrenia is a neuropsychiatric illness characterized by impairments in cognition and positive and negative symptoms. As currently used antipsychotics do not treat all symptoms of the disease, further research of the therapeutic potential of various drugs in the treatment of this disease is crucial. Psychosis is a condition or a mental state that usually accompany schizophrenia, as well as other disorders. We used MK-801, a non-competitive antagonist of NMDA receptors to induce an experimental model of psychosis in rats. By binding to the NMDA subtype of glutamate receptors located on inhibitory interneurons, MK-801 has been shown to elicit an overactivation of cortical and hippocampal pyramidal neurons, leading to behaviors such as hyperlocomotion, stereotypy or cognitive impairments. LY 379268, an agonist of group II metabotropic glutamate receptors, binds to both presynaptic and postsynaptic receptors on pyramidal neurons. It has been suggested that it could alleviate the MK-801-induced hyperactivity of the principal neurons. In this study, we sought to demonstrate the effects of LY 379268 in the MK-801 animal model of psychosis and hypothesized that LY 379268 will ameliorate deficits in the reversal learning induced by MK-801. Materials and methods: Long Evans rats received...
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Mnemonic and behavioural effects of biperiden, an M1-selective antagonist, in the rat
Popelíková, Anna ; Stuchlík, Aleš (advisor) ; Telenský, Petr (referee)
Due to the persisting lack of reliable animal models of cognitive impairment with good translational validity, researches strive to discover new ways and tools to replicate symptoms of human neurodegenerative diseases in rodents. Recently, biperiden, an M1- selective muscarinic antagonist, has been proposed as a potential tool for generating fast screening models of mnemonic deficits such as seen in patients with Alzheimer's disease. Being highly selective for the M1 receptor, a predominant type of muscarinic acetylcholine receptors in the brain involved in cognitive processes, it has been speculated to possibly only influence cognition without causing sensorimotor side effects. Studies assessing the usability of this drug reported conflicting results. We have decided to expand the experimental data and evaluate biperiden's validity in several variants of the Morris water maze. The results of this study showed no significant effect of biperiden on cognitive flexibility, tested by reversal learning. In delayed-matching-to-position paradigm, which tests assesses working memory, we found a difference in performance between the two experimental groups; however, it cannot be unequivocally attributed to a memory impairment. No effects were observed in visible platform task, confirming a lack of...
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Separation of hippocampal function in Morris water maze and in active place avoidance by alternance protocol
Vojtěchová, Iveta ; Petrásek, Tomáš (advisor) ; Hiadlovská, Zuzana (referee)
In this work, we examined the executive functions of the hippocampus at the behavioral level as a so-called behavioral separation in adult rats. We studied an impact of day-to-day alternation versus sequential learning (and the order of learning) of two spatial tasks (Morris Water Maze and Active Allothetic Place Avoidance) testing different hippocampal functions (experiment 1), or an impact of sequential versus alternating learning of one task (Active Allothetic Place Avoidance) in two different rooms (experiment 2), on performance. We found out that rats are able to learn both tasks as well as to discriminate between the two contexts regardless of the order or alternating of learning. Because such executive functions are impaired in human patients suffering from schizophrenia, we used this procedure also in the rat model of schizophrenia induced by acute intraperitoneal application of dizocilpine (MK-801), glutamate NMDA receptors antagonist, in the dose of 0.08 mg/kg. We failed to selectively disrupt the behavioral separation, however, we observed general learning deficit and hyperlocomotion regardless of the alternation in the Active Allothetic Place Avoidance task in these rats. The cognitive impairments in connection with learning after such low dose of MK-801 in this task have not yet been...
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Inhibitors of axonal regeneration and their importance for neuroplasticity, behaviour and memory
Vojtěchová, Iveta ; Petrásek, Tomáš (advisor) ; Hock, Miroslav (referee)
The central nervous system of higher vertebrates, in contrast to the peripheral one, doesn't regenerate. That is because of the presence of many growth inhibitors produced by a glial scar and oligodendrocytes; the most important inhibitors are MAG (myelin-associated glycoprotein), OMgp (oligodendrocyte-myelin glycoprotein) and mainly Nogo protein. Nogo-A is one of three isoforms of the Nogo protein located primarily in the brain and the spinal cord where it causes the degradation of growth cones, inhibits the growth of neurites, restricts the neuroplasticity and prevents the regeneration of injured axons in adulthood. The Nogo receptor complex serves for a reception of signals and the following signal cascade causes the destabilisation of actin filaments. There are also other receptors for Nogo-A, e. g. the PirB receptor. During the development, Nogo-A is highly expressed by neurons but in adulthood, the main producers are oligodendrocytes. It is noteworthy, that neuronal expression of Nogo-A doesn't decrease after birth in structures with high plasticity, e. g. in the hippocampus which is important especially for spatial learning and memory. In the hippocampus, Nogo-A keeps a balance between the synaptic plasticity and stability and restricts the long-term potentiation. Therefore, this bachelor's thesis...
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