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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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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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Flexibility in spatial cognition of rat
Staňková, Anna ; Svoboda, Jan (advisor) ; Telenský, Petr (referee)
5 Abstract Cognitive flexibility is an ability to adapt a behavior according to a dynamic changes in an environment. It belongs to executive functions, along with the processes of working memory, attention, motivation and others. Flexibility is important in the process of changing "stimulus-response" contingency at the time when the initial stimulus no longer leads to reward. According to the nature of the changes we can distinguish three types of cognitive flexibility: reversal learning, intradimensional set shifting and extradimensional set shifting. The processes of cognitive flexibility take place in fronto-striato-thalamic circuit with numerous connections to other brain regions, especially the limbic system. Deficit in cognitive flexibility belongs among cognitive symptoms of schizophrenia, a psychiatric illness we studied in the experimental part of this work using its analogue in rat. The aim of the experimental work was to test cognitive flexibility deficit in the rat model of schizophrenia-like behavior in the Carousel maze in four versions of task with different cognitive load. Animal model of schizophrenia was induced by acute administration of non-competitive NMDA receptor antagonist MK-801 at doses of 0.05 and 0.10 mg/kg i.p. Reversal learning was not damaged in this type of task following the...
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