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Regeneration and structural changes of the nerve tissue after the extracellular matrix modification
Vallová, Jana ; Machová Urdzíková, Lucia (advisor) ; Hampl, Aleš (referee) ; Hubálek Kalbáčová, Marie (referee)
Regeneration and structural changes of the nerve tissue after the extracellular matrix modification. Abstract ECM modification may contribute to changes in nerve tissue plasticity. Therefore, 4- methylubulliferone is used in our study, which disrupted the structure of the perineuronal networks surrounding some types of neurons responsible for the formation of memory traces. Mice were fed a 4-MU diet (6.7 mg / g / day) for 6 months, which improved their memory skills in a spontaneous recognition test without a significant adverse effect on the kidneys, liver, or joints.In the next part of the study, an extracellular matrix (UC-ECM) was derived from fetal human umbilical cord tissue also generated as biomimetic hydrogel. Due to the generated UC-ECM's low stability and rapid degradation, the structure was stabilized by covalent genipin bonding. Stabilization with 1 mM genipine increased the biological stability of the material. UC-ECM as well as ECM/G didn't show toxicity in vitro in mesenchymal stem cell proliferation; axonal budding or neural stem cell growth and differentiation were not adversely affected. The biocompatibility of both materials was verified in vivo by applying the material to an intracortical photothrombotic rat lesion, where gelation and infiltration of the lesion and hydrogel by host...
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Matching the role of chondroitin sulphate proteoglycan, aggrecan, in dense extracellular matrix of perineuronal nets and glial scar
Gmiterková, Lenka ; Růžička, Jiří (advisor) ; Telenský, Petr (referee)
Traumatic brain and spinal cord injuries are worldwide medical problems. Disruption of the tissue leads to the changes in the cellular and extracellular matrix composition. This newly formed scar is not permissive for the axonal regrowth. Its function in prohibiting neuronal plasticity is similar to the perineuronal nets present in undamaged brain. One of the key components of both perineuronal nets and scar is proteoglycan aggrecan. In this thesis I focused on the function of aggrecan in central nervous system, mechanism of its growth inhibitory feature and research in the field of traumatic brain or spine cord injury treatment. It is important topic, since currently there are not any approved human therapies to recover axonal growth at the site of formed scar.
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The effect of structural changes in perineuronal nets and deep cooling on synaptic plasticity and memory of tauopathy mice
Šafránková, Kristýna ; Růžička, Jiří (advisor) ; Telenský, Petr (referee)
Tauopathy is accompanied by both loss of neurons and synapses. The neuronal loss is irreversible with very low chance of functional replacement therapy. However, lost synapses could be restored with proper stimuli. Perineuronal nets (PNNs) are serving as a protecting barrier for neurons, on the other hand they are significantly decreasing the synaptic plasticity. Temporary disintegration of the PNNs by enzymatic therapy might lead to rewiring and accelerate processes of memory and learning. Model of Cold Induced plasticity leads to the withdrawal of significant number of synapses across the brain. The recovery of these could be followed in healthy and diseased animals. Moreover, it can stimulate Cold shock protein dependent neuroprotective mechanisms. This master thesis is focused on these two forms of synaptic plasticity models; forced remodeling of PNNs and model of cold induced synaptic plasticity. Both will serve as a tool to modulate processes of memory and learning in the P301S tauopathy, in mice. In detail, the work will follow changes in the number of synapses at the region of CA1 of hippocampus and synaptic protein levels at level of whole hippocampus and behavioral recovery of pre-trained long-term memory task dependent on dorsal hippocampus. Key words: Perineuronal nets, aggrecan,...
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The effect of structural changes in perineuronal nets and deep cooling on synaptic plasticity and memory of tauopathy mice
Šafránková, Kristýna ; Růžička, Jiří (advisor) ; Telenský, Petr (referee)
Tauopathy is accompanied by both loss of neurons and synapses. The neuronal loss is irreversible with very low chance of functional replacement therapy. However, lost synapses could be restored with proper stimuli. Perineuronal nets (PNNs) are serving as a protecting barrier for neurons, on the other hand they are significantly decreasing the synaptic plasticity. Temporary disintegration of the PNNs by enzymatic therapy might lead to rewiring and accelerate processes of memory and learning. Model of Cold Induced plasticity leads to the withdrawal of significant number of synapses across the brain. The recovery of these could be followed in healthy and diseased animals. Moreover, it can stimulate Cold shock protein dependent neuroprotective mechanisms. This master thesis is focused on these two forms of synaptic plasticity models; forced remodeling of PNNs and model of cold induced synaptic plasticity. Both will serve as a tool to modulate processes of memory and learning in the P301S tauopathy, in mice. In detail, the work will follow changes in the number of synapses at the region of CA1 of hippocampus and synaptic protein levels at level of whole hippocampus and behavioral recovery of pre-trained long-term memory task dependent on dorsal hippocampus. Key words: Perineuronal nets, aggrecan,...
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Matching the role of chondroitin sulphate proteoglycan, aggrecan, in dense extracellular matrix of perineuronal nets and glial scar
Gmiterková, Lenka ; Růžička, Jiří (advisor) ; Telenský, Petr (referee)
Traumatic brain and spinal cord injuries are worldwide medical problems. Disruption of the tissue leads to the changes in the cellular and extracellular matrix composition. This newly formed scar is not permissive for the axonal regrowth. Its function in prohibiting neuronal plasticity is similar to the perineuronal nets present in undamaged brain. One of the key components of both perineuronal nets and scar is proteoglycan aggrecan. In this thesis I focused on the function of aggrecan in central nervous system, mechanism of its growth inhibitory feature and research in the field of traumatic brain or spine cord injury treatment. It is important topic, since currently there are not any approved human therapies to recover axonal growth at the site of formed scar.
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The role of link proteins in the stabilization of the brain extracellular matrix and in formation and maintaining of the perineuronal nets
Suchá, Petra ; Vargová, Lýdia (advisor) ; Jendelová, Pavla (referee)
The brain extracellular space (ECS) contains specified macromolecules forming the extracellular matrix (ECM), containing a high amount of negative charges that could bind water or other soluble ions and molecules diffusing within the ECS. In specific brain areas, the ECM molecules form a condensed, reticular-like structure of perineuronal nets (PNNs). It has been found that PNNs appear at the end of the critical period, when they stabilize the synapses and terminate their plasticity and may have also neuroprotective function. To study the role of brain link protein 2 (Bral2) in stabilizing the ECM complexes, we employed the real-time iontophoretic method and immunohistochemical analysis to show the difference in the ECS diffusion parameters and level of expression of the ECM molecules between the wild type and Bral2-deficient mice. We also compared changes in the ECS diffusion parameters induced by Bral2 deficiency with those appeared after enzymatic destruction of the ECM by the chondroitinase ABC (chABC). In the Bral2-deficient mice, we discovered significantly decreased values of tortuosity in the trapezoid body. This difference was age related and did not manifest itself in young mice. Immunohistochemical analysis showed that inferior colliculus does not contain Bral2-brevican based...
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