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Memory and cognitive coordination impairment in rat models of neuropsychiatric diseases
Vojtěchová, Iveta ; Stuchlík, Aleš (advisor) ; Syka, Josef (referee) ; Hort, Jakub (referee)
The memory and spatial navigation are extremely important brain functions for humans, but they are often the question of life and death for animals. In humans, memory can be disrupted by various neuropsychiatric disorders. The patients suffering from Alzheimer's dementia (AD) have impaired working and long-term memory, spatial navigation, higher cognitive functions and social memory. The deficit of cognitive coordination (the skill to recognize the relevancy of incoming information) and disorientation belong to the symptomatology of schizophrenia. Intelectual disability appears in some patients with autism spectrum disorder. Unfortunately, it is not possible to cure these disorders efficiently because the etiology is not known in the majority of patients. The causes leading to development of these disorders could be revealed using animal models. This thesis contributes to the characterization of the cognitive skills disruptions - as well as other behavioral alterations - in selected rat models of AD (transgenic McGill rat, non-transgenic Samaritan rat) and schizophrenia (lipopolysaccharide model of early postnatal, or prenatal, bacterial infection). The thesis also discusses the validity and limitations of these models. Our results showed a severe deficit of spatial navigation, learning and...
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Learning and memory in Nogo-A knockdown rats
Petrásek, Tomáš
The Nogo-A protein belongs among the most important regulatory molecules in the brain, regulating development of neuronal and glial cells, axon guidance and adult synaptic plasticity. Although it has been studied mainly as an obstacle to axon regeneration after CNS injury, it plays a role in many pathological conditions, including neurodegenerative and neuropsychiatric diseases. This work offers a literature review of the current knowledge about functions of Nogo-A and related proteins, and then recapitulates the results of experiments focused on the impact on decreased expression of Nogo-A on behavior in a transgenic rat model. The most important finding is that the Carousel Maze performance, tapping higher cognitive functions such as cognitive coordination and cognitive flexibility, is remarkably impaired in this model, while other cognitive functions, such as spatial navigation and both spatial and non-spatial memory are spared in the Nogo-A deficient rats. The results are discussed in the context of a hypothesis linking Nogo-A mutations or abnormal expression to human schizophrenia. We conclude that the Nogo-A deficient rats constitute a very promising animal model of schizophrenia and deserve further attention.
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Learning and memory in Nogo-A knockdown rats
Petrásek, Tomáš ; Stuchlík, Aleš (advisor) ; Zach, Petr (referee) ; Rokyta, Richard (referee)
The Nogo-A protein belongs among the most important regulatory molecules in the brain, regulating development of neuronal and glial cells, axon guidance and adult synaptic plasticity. Although it has been studied mainly as an obstacle to axon regeneration after CNS injury, it plays a role in many pathological conditions, including neurodegenerative and neuropsychiatric diseases. This work offers a literature review of the current knowledge about functions of Nogo-A and related proteins, and then recapitulates the results of experiments focused on the impact on decreased expression of Nogo-A on behavior in a transgenic rat model. The most important finding is that the Carousel Maze performance, tapping higher cognitive functions such as cognitive coordination and cognitive flexibility, is remarkably impaired in this model, while other cognitive functions, such as spatial navigation and both spatial and non-spatial memory are spared in the Nogo-A deficient rats. The results are discussed in the context of a hypothesis linking Nogo-A mutations or abnormal expression to human schizophrenia. We conclude that the Nogo-A deficient rats constitute a very promising animal model of schizophrenia and deserve further attention. Powered by TCPDF (www.tcpdf.org)
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Protective effect of pro-cognitive training during adolescence on neuronal coordination deficit in a pharmacological model of schizophrenia.
Krajčovič, Branislav ; Kubík, Štěpán (advisor) ; Bendová, Zdeňka (referee)
Schizophrenia is a severe neuropsychiatric disorder characterized by positive, negative and cognitive symptoms with poor functional outcomes, placing an enormous burden on the individual, caregivers and society. Although deficits in cognition are an integral part of the disease and the best predictor of functional outcomes, there is as yet no established treatment addressing them. Avoidance of a hidden place on a continuously rotating arena (Carousel) requires cognitive control and is a rodent model of cognitive coordination of information from dissociated spatial frames, which is impaired in acute pharmacological and neurodevelopmental model of schizophrenia. Cognitive training on the Carousel during adolescence alleviates adult cognitive deficit in a neurodevelopmental model of schizophrenia and improves neural coordination (oscilations in the beta and gamma band), which is thought to be necessary for cognition. We examined if cognitive training during adolescence eliminates the deficit in neuronal coordination observed in adult rats after acute systemic NMDA receptor antagonist MK-801 (0.15 mg/kg). During adolescence, rats were either trained in spatial avoidance on Carousel or merely handled. As adults, rats received two 5-min exploration sessions in the same (A/A) or in two distinct...
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Learning and memory in Nogo-A knockdown rats
Petrásek, Tomáš
The Nogo-A protein belongs among the most important regulatory molecules in the brain, regulating development of neuronal and glial cells, axon guidance and adult synaptic plasticity. Although it has been studied mainly as an obstacle to axon regeneration after CNS injury, it plays a role in many pathological conditions, including neurodegenerative and neuropsychiatric diseases. This work offers a literature review of the current knowledge about functions of Nogo-A and related proteins, and then recapitulates the results of experiments focused on the impact on decreased expression of Nogo-A on behavior in a transgenic rat model. The most important finding is that the Carousel Maze performance, tapping higher cognitive functions such as cognitive coordination and cognitive flexibility, is remarkably impaired in this model, while other cognitive functions, such as spatial navigation and both spatial and non-spatial memory are spared in the Nogo-A deficient rats. The results are discussed in the context of a hypothesis linking Nogo-A mutations or abnormal expression to human schizophrenia. We conclude that the Nogo-A deficient rats constitute a very promising animal model of schizophrenia and deserve further attention.
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Impaired cognitive coordination on a rotating arena after systemic dizocilpine (MK-801).
Buchtová, Helena ; Kubík, Štěpán (advisor) ; Olexová, Lucia (referee)
Disruption of cognitive abilities such as learning, memory and spatial navigation accompanies a number of neuropsychiatric disorders including schizophrenia. Cognitive symptoms are also most difficult to target by available pharmacotherapy.. Behavioral and molecular evidence point to a disruption of NMDA receptors and glutamatergic and dopaminergic neurotransmission. Impaired cognitive coordination has been proposed as a core cognitive deficit in schizophrenia. Non- competitive NMDAR antagonists are used to model schizophrenia- related symptoms in humans and in experimental animals. Place avoidance on a rotating arena is used to model cognitive functions disrupted in an animal model of schizophrenia. The goal of this thesis is to show whether the deficit in place avoidance is due to disrupted cognitive coordination or another effect of NMDAR antagonism such as hyperlocomotion, general learning deficit, or altered sensitivity.
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Existence of alternative strategies and effect of habituation in the solution of the Place Avoidance Task
Okruhlicová, Šárka ; Klement, Daniel (advisor) ; Nedvídek, Jan (referee)
Active allothetic avoidance task (AAPA) could be a useful tool to study cognitive deficit of schizofrenia. In this task two different reference frames are created. The subject should distinguish which oriental frame is relevant for navigation and is proper for the solution of the task. This ability is called cognitive coordination. It is proved that the process of cognitive coordination is impaired in schizophrenic individuals, which comes to light in a Stroop test. Schizophrenia-like behavior can be modelled on the rats by a non-competitive NMDA receptor antagonist dizocipline (MK-801). The aim of these thesis was to study the existence of alternative strategies and the influence of different habituation on the performance of rats within AAPA. Furthermore, we have been studying the influence of MK-801 at a dose of 0.15mg / kg on the cognitive coordination in this task. We have found that the rats are able to learn AAPA task after pre-training without distal orientation cues, using relatively efficient alternative strategies. In these alternative strategies the idiothetic navigation is applied. The performance of rats in AAPA task is influenced by different conditions during habituation. We have proved that MK-801 at this dosage has no effect on cognitive performance of the rats in AAPA task, but...
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Learning and memory in Nogo-A knockdown rats
Petrásek, Tomáš ; Stuchlík, Aleš (advisor) ; Zach, Petr (referee) ; Rokyta, Richard (referee)
The Nogo-A protein belongs among the most important regulatory molecules in the brain, regulating development of neuronal and glial cells, axon guidance and adult synaptic plasticity. Although it has been studied mainly as an obstacle to axon regeneration after CNS injury, it plays a role in many pathological conditions, including neurodegenerative and neuropsychiatric diseases. This work offers a literature review of the current knowledge about functions of Nogo-A and related proteins, and then recapitulates the results of experiments focused on the impact on decreased expression of Nogo-A on behavior in a transgenic rat model. The most important finding is that the Carousel Maze performance, tapping higher cognitive functions such as cognitive coordination and cognitive flexibility, is remarkably impaired in this model, while other cognitive functions, such as spatial navigation and both spatial and non-spatial memory are spared in the Nogo-A deficient rats. The results are discussed in the context of a hypothesis linking Nogo-A mutations or abnormal expression to human schizophrenia. We conclude that the Nogo-A deficient rats constitute a very promising animal model of schizophrenia and deserve further attention. Powered by TCPDF (www.tcpdf.org)
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Using the Carousel Maze as a test of cognitive symptoms in an animal model of schizophrenia
Buchtová, Helena ; Landová, Eva (advisor) ; Jiruška, Přemysl (referee)
Spatial behaviour of animals is used to model cognitive human abilities such as declarative learning and memory. Cognitive deficits accompany a number of neuropsychiatric disorders and their treatment is most problematic. Schizophreniais one of these disorders. Behavioral, neurochamical, and molecular evidence point to a critical role of the NMDA glutamatergic receptors in the pathogenesis of schizophrenia. Disruption of their function results in behavioral and physiological changes including dysregulation of the depaminergic neurotransmission. This fact is used to model schizophrenia-related symptoms by systemic administration of NMDA receptor antagonists. Models combining administration of these drugs with behavioral tests aimed at specific cognitive deficits are of particular interest. This thesis use existing evidence to show that the Carousel Maze is such a behavioral test, which uses dynamic spatial learning to test the ability to coordinate discordant information and specific use of the relevant cues.
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