|
|
Mitochondrial dysfunction in brain tumors
Rollerová, Kateřina ; Vaňátko, Ondřej (advisor) ; Zobalová, Renata (referee)
Brain tumors are one of the most serious pathologies of the central nervous system. Brain tumors are aggressive and very hard to treat due to the fragile nature of the nervous system, presence of blood-brain barrier and high recurrence rate. One of the hallmarks of brain tumors is mitochondrial dysfunction. Mitochondria are organelles involved in essential cellular processes, such as energy production, redox and calcium signaling, or the regulation of cell death. Structural and functional abnormalities, mutations in the mitochondrial genome and other mitochondrial dysregulations may cause disruptions in various cellular processes, such as production of reactive oxygen species, migration, proliferation, or regulation of cell death, promoting the development and/or maintenance of brain tumors. The goal of this thesis is to summarize current knowledge about mitochondrial dysfunction in brain tumors. Key words: brain tumors; mitochondria; mitochondrial dysfunction; Warburg effect; apoptosis; reactive oxygen species; isocitrate dehydrogenase
|
|
|
Identification of changes in membrane properties of astrocytes in a mouse model of amyotrophic lateral sclerosis
Vaňátko, Ondřej ; Turečková, Jana (advisor) ; Vlachová, Viktorie (referee)
Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder of the central nervous system characterized by loss of motor neurons and voluntary muscle degeneration. Astrocytes play a major role in regulation of the disease onset and progression due to their intimate association with neurons. Regulation of ionic homeostasis is one of their key functions and its failure has been linked to several neurological diseases. The aim of this thesis was to explore differences in membrane properties of astrocytes in ALS. To fulfill this aim, a double transgenic mouse strain with ALS-like phenotype and a specific expression of enhanced green fluorescent protein in astrocytes was generated. To phenotype this strain, two sensorimotor tests, wire grid hang test and rotarod test, were conducted. Immunohistochemistry was used to characterize the strain on a cellular level and to explore changes of specific ion channels. Functional properties of astrocytes were explored using the patch clamp technique. The double transgenic strain has the characteristic ALS-like phenotype and is comparable to the original strain with differences in symptom onset and progression between models and sexes. On the cellular level, there are characteristic ALS features, specifically loss of motor neurons and astrogliosis....
|
|
|
Glial cells and their role in amyotrophic lateral sclerosis
Vaňátko, Ondřej ; Anděrová, Miroslava (advisor) ; Černý, Jan (referee)
Amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) is a progressive neurodegenerative disorder. It affects upper and lower motor neurons in the brain motor cortex, the brain stem and the spinal cord, causing their death, which results in denervation of voluntary muscles. Progressive muscle weakness and atrophy throughout the entire body gradually leads to worsening of the ability to move, speak, chew, swallow and eventually breath. Ultimately it results in affected individual's death due to respiratory muscle failure. Although first identified in 1869, no cure for ALS has been yet found. While early studies focused mainly on the research of motor neurons themselves, the attention has shifted towards glial cells in the past two decades. Glial cells are essential for proper neuron functioning and survival and it appears that they play a major role in ALS progression. The goal of this thesis is to review and summarize findings on the role of glial cells in ALS over the last years, focusing on four specific types of glial cells, namely astrocytes, microglia, oligodendrocytes and NG2-glia. Key words: amyotrophic lateral sclerosis, ALS, motor neuron, glia, astrocyte, microglia, oligodendrocyte, NG2-glia
|
guest ::
