|
|
The effect of immunosupression on cell therapy in mouse model of Alzeimer's disease
Gajdoš, Roman ; Jendelová, Pavla (advisor) ; Chmelová, Martina (referee)
Alzheimer's disease is a chronic, progressive, neurodegenerative disease. It belongs to the most common type of dementia and worldwide it is statistically the fifth cause of mortality. The most common morphological markers are insoluble β amyloid plaques, hyperphosforylated tau proteins and formation of neurofibrilar tangles. Among the manifestations of the disease is amyloid angiopathy, synaptic transmission disorders and subsequent apoptosis, deterioration of cognitive functions and brain atrophy. Studies have shown that administration of mesenchymal stem cells (MSC) has an immunomodulatory effects and it can reduce the production and storage of β amyloid and thus improve cognitive functions. In preclinical studies, which are conducted in transgenic mice and often use xenografts, administration of immunosuppresion may lead to variety of positive or negative effects which can affect the results of the experiment. The subject of the master's thesis was to determine the effect of immunosuppression on experimental therapy with MSC in various time windows of AD progression (model 3xTg). At which scale and combination of immunosupression will influence the cell therapy's effects, the length of graft survival, mortality of experimental animals and changes at the cellular level. We have also assessed...
|
|
|
The effect of immunosupression on cell therapy in mouse model of Alzeimer's disease
Gajdoš, Roman ; Jendelová, Pavla (advisor) ; Chmelová, Martina (referee)
Alzheimer's disease is a chronic, progressive, neurodegenerative disease. It belongs to the most common type of dementia and worldwide it is statistically the fifth cause of mortality. The most common morphological markers are insoluble β amyloid plaques, hyperphosforylated tau proteins and formation of neurofibrilar tangles. Among the manifestations of the disease is amyloid angiopathy, synaptic transmission disorders and subsequent apoptosis, deterioration of cognitive functions and brain atrophy. Studies have shown that administration of mesenchymal stem cells (MSC) has an immunomodulatory effects and it can reduce the production and storage of β amyloid and thus improve cognitive functions. In preclinical studies, which are conducted in transgenic mice and often use xenografts, administration of immunosuppresion may lead to variety of positive or negative effects which can affect the results of the experiment. The subject of the master's thesis was to determine the effect of immunosuppression on experimental therapy with MSC in various time windows of AD progression (model 3xTg). At which scale and combination of immunosupression will influence the cell therapy's effects, the length of graft survival, mortality of experimental animals and changes at the cellular level. We have also assessed...
|
|
|
Modulation of memory using enzymatic digestion of perineuronal nets in perirhinal cortex
Procházková, Natálie ; Jendelová, Pavla (advisor) ; Chmelová, Martina (referee)
In the adult brain, neuronal plasticity is regulated by a specialized structure of extracellular matrix, the perineuronal nets (PNNs), which restrict synaptic plasticity by binding molecules of inhibitory nature and posing as a physical barrier to alterations in neuronal connectivity. This effect is abolished by removal of PNNs by the enzyme chondroitinase ABC (chABC), which enables to reopen critical period window and leads to memory improvement. Here, we utilized chABC and a novel approach in removing the PNNs in perirhinal cortex, using the enzyme hyaluronidase (Hyase), to assess differences in the use of these enzymes in object recognition (OR) memory improvement and alterations in the structure of neuronal network of wild type mice. Our findings suggest that Hyase may be a more convenient tool to PNN removal than chABC, as Hyase surpasses chABC in promoting the OR memory, influence larger portion of neuronal network by affecting both inhibitory and excitatory neurons, and provides extended temporal window for experimental modulation of activity-dependent synaptic plasticity. Key words: perineuronal nets, synaptic plasticity, chondroitinase ABC, hyaluronidase, perirhinal cortex, memory
|
|
|
Central nervous system plasticity in adulthood and after injury.
Procházková, Natálie ; Jendelová, Pavla (advisor) ; Chmelová, Martina (referee)
Perineural nets are a structure of extracellular matrix, enwrapping several subpopulations of neurons in the central nervous system. Their formation is linked to the closure of critical period and significant plasticity restriction. In a healthy organism, they are important for stabilisation of mature nervous system, support of highly active neurons, and neuroprotection. However, they are one of the factors that restrict tissue regeneration during pathological conditions by participating in the formation of glial scar and upregulating molecules that have inhibitory impact on neuron sprouting. Digestion of perineuronal nets, which is mostly achieved enzymatically, leads to re-opening of critical period and renewal of plasticity, potentiating neuronal sprouting and growth and overall regeneration of central nervous system after mechanical damage, such as spinal cord injury, or during neurodegenerative diseases, as is Alzheimer's disease. Perineural nets play a similar role in Alzheimer's disease and aging, where they participate in memory loss. Renewal of plasticity in these conditions leads to facilitation of synaptic transmission and therefore eliminating the memory deficit. Key words: neurodegenerative diseases, CNS injury, Alzheimer's disease, perineural nets, chondroitinsulfate proteoglycans
|
guest ::
RSS feed.