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The role of microglia and astrocytes in Alzheimer's disease
Pospíšilová, Eva ; Telenský, Petr (advisor) ; Svoboda, Jan (referee)
Alzheimer's disease is a neurodegenerative disease that affects the central nervous system and is characterized mainly by problems with memory abilities. With the more aging population, the number of patients with this disease is gradually increasing, so Alzheimer's disease research is becoming one of the main priorities of today's health care. Although the research has been going on for more than a century, the exact causes of the Alzheimer's disease are still unclear. For a long time, the main role was attributed to the pathology of amyloid β and tau protein, the basic pathophysiological features of this disease, but in recent years, it has become clear that microglia and astrocytes also play an important role. These glial cells affect the amount of amyloid β and the hyperphosphorylated tau protein, but they are also crucial for maintaining homeostasis of the central nervous system. Activation of microglia and astrocytes in Alzheimer's disease can lead to disruption of the physiological functions of these neuroglia, and thus to problems with the removal of amyloid and tau protein, but also to the induction of chronic neuroinflammation. This work aims to summarize and organize the basic knowledge about the role of microglia and astrocytes in Alzheimer's disease, while focusing mainly on their role...
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název v anglickém jazyce není uveden
Pospíšilová, Eva ; Paleček, Jiří (advisor) ; Kršiak, Miloslav (referee) ; Rokyta, Richard (referee)
Tissue injury leads to increased sensitivity to noxious and innocuous stimuli due to mechanisms of peripheral sensitisation of primary nociceptors and central sensitization of neurons in the spinal dorsal horns. The subpopulation of capsaicin - sensitive sensory neurons plays an important role in this process. The capsaicin - sensitive neurons express capsaicin TRPV1 receptors (transient receptor potential 1) on their peripheral and central terminals, local high concentration capsaicin treatment can induce regional destruction of these endings. It is well estabilished that TRPV1 receptors play the key role in neural transmission of nociceptive information and its modulation. The aims of this study were to investigate the role of capsaicin - sensitive primary afferent fibers and the involvement of peripheral and central TRPV1 receptors in the development of hypersensitivity after surgical tissue trauma, to test the effect of high concentration capsaicin and the specific TRPV1 antagonist treatment on postoperative pain and to enlighten the function of central TRPV1 receptors in the neural mechanisms of nociception. Using behavioral testing methods, the responses to mechanical (Von Frey filaments) and thermal stimuli (radiant heat source) were tested on the rat plantar incision model of surgical pain...
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Adenylate cyclase toxin of bacteria Bordetella pertussis: mechanism of potassium efflux from macrophages
Pospíšilová, Eva ; Mašín, Jiří (advisor) ; Konopásek, Ivo (referee)
The adenylate cyclase toxin-hemolysin (ACT or CyaA) is a key virulence factor of Bordetella pertussis, the agent of the human respiratory disease whooping cough. CyaA penetrates phagocytes expressing the CD11b/CD18 integrin and exhibits two different activities. One toxin conformer oligomerizes in cell membrane and permeabilizes it by forming small cation-selective pores. Another toxin conformer appears to act as monomer. It forms a calcium influx path in the membrane, concomitantly with translocating into cells the adenylate cyclase enzyme domain that binds calmodulin and catalyzes unregulated conversion of cytosolic ATP into cAMP. We show here that CyaA causes efflux of K+ from CD11b+ cells by a mechanism that requires binding of CyaA to integrin CD11b/CD18 and permeabilization of the cellular membrane by pore-forming conformer of CyaA. Intact CyaA and the enzymatically inactive CyaA-AC- toxoid unable to generate cAMP produced the same kinetics of K+ efflux showing that elevation or signaling of cAMP had no role in this activity. The truncated CyaA variant (CyaA-AC) devoid of its invasive AC domain failed to promote K+ efflux despite a normal pore forming activity on erythrocyte and artificial membranes. However, binding of the MAb 3D1, which recognizes the distal segment of the AC domain...
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Comparison of activation lower limb muscules in slide turn and turn in telemark position
Pospíšilová, Eva ; Jindra, Matouš (advisor) ; Chrástková, Martina (referee)
Title: Comparison of activation of lower limb muscles in a slide turn and in a telemark position turn. Objectives: The aim of this theses is to compare the muscle activation of selected muscles of the lower limbs in the slide turn and in the telemark technique. Methods: The muscle activation of selected muscles was measured during skiing using surface EMG. All probands crossed the track in two ways. The first one was the telemark technique and the second one the middle slide turn technique. The received signal from each ride was processed and evaluated. The results of both rides were compared to each other. Results: We found differences in the order of muscle activation between telemark and slide turn. We did not find unequivocal motion for each technique, which we could be compared to each other. Each probe had a different individual order of muscle activation in each technique. Keywords: downhill skiing, telemark, EMG, muscle activation
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Argument semantics and relative frequency in the comprehension of the passive construction in persons with aphasia
Pospíšilová, Eva ; Láznička, Michal (advisor) ; Chromý, Jan (referee)
This bachelor thesis deals with the influence of argument semantics and relative frequency of passive voice on the understanding of Czech passive construction in people with aphasia. The aim of the work is to design an experiment that will examine the factors connected with the agrammatic understanding in Czech, and test it on a group of neurotypic speakers. Theoretical chapters of this thesis are devoted to a general description of aphasia, linguistic aphasiology and manifestations of aphasic syndromes in Czech. They also present the basic results of previous research which examined the understanding of semantically reversible passive sentences in patients with aphasia. In the final theoretical chapter, findings from foreign aphasiological literature, which highlighted the relationship between the level of understanding of complex syntactic structures and their frequency, are discussed. The experimental part of the text focuses on the design of the actual experiment. Based on a corpus analysis, a total of 24 verbs with high and low relative frequency of passive forms were selected, each verb was used in four sentences with different combinations of voice, relative frequency of passive and (in)animacy of patient. To verify comprehension, the self-paced reading method was chosen along with...
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Adenylate cyclase toxin of bacteria Bordetella pertussis: mechanism of potassium efflux from macrophages
Pospíšilová, Eva ; Mašín, Jiří (advisor)
The adenylate cyclase toxin-hemolysin (ACT or CyaA) is a key virulence factor of Bordetella pertussis, the agent of the human respiratory disease whooping cough. CyaA penetrates phagocytes expressing the CD11b/CD18 integrin and exhibits two different activities. One toxin conformer oligomerizes in cell membrane and permeabilizes it by forming small cation-selective pores. Another toxin conformer appears to act as monomer. It forms a calcium influx path in the membrane, concomitantly with translocating into cells the adenylate cyclase enzyme domain that binds calmodulin and catalyzes unregulated conversion of cytosolic ATP into cAMP. We show here that CyaA causes efflux of K+ from CD11b+ cells by a mechanism that requires binding of CyaA to integrin CD11b/CD18 and permeabilization of the cellular membrane by pore-forming conformer of CyaA. Intact CyaA and the enzymatically inactive CyaA-AC- toxoid unable to generate cAMP produced the same kinetics of K+ efflux showing that elevation or signaling of cAMP had no role in this activity. The truncated CyaA variant (CyaA-AC) devoid of its invasive AC domain failed to promote K+ efflux despite a normal pore forming activity on erythrocyte and artificial membranes. However, binding of the MAb 3D1, which recognizes the distal segment of the AC domain...
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Comparison of activation lower limb muscules in slide turn and turn in telemark position
Pospíšilová, Eva ; Jindra, Matouš (advisor) ; Chrástková, Martina (referee)
Title: Comparison of activation of lower limb muscles in a slide turn and in a telemark position turn. Objectives: The aim of this theses is to compare the muscle activation of selected muscles of the lower limbs in the slide turn and in the telemark technique. Methods: The muscle activation of selected muscles was measured during skiing using surface EMG. All probands crossed the track in two ways. The first one was the telemark technique and the second one the middle slide turn technique. The received signal from each ride was processed and evaluated. The results of both rides were compared to each other. Results: We found differences in the order of muscle activation between telemark and slide turn. We did not find unequivocal motion for each technique, which we could be compared to each other. Each probe had a different individual order of muscle activation in each technique. Keywords: downhill skiing, telemark, EMG, muscle activation
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The effect of nerolidol nad valencene on the efficacy of 5-fluorouracil in colon cancer cells
Pospíšilová, Eva ; Skálová, Lenka (advisor) ; Hanušová, Veronika (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Eva Pospíšilová Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The effect of nerolidol nad valencene on the efficacy of 5- fluorouracil in colon cancer cells The cancer diseases belong among the most serious diseases on the world. Cytostatics, which are used for treatment, have many side effects and there is a high occurrence of resistance. Therefore scientists are looking for appropriate substances for the combination therapy. Sesquiterpenes, secondary metabolites of plants, could be one of the options. The aims of this work were to study the influence of cytostatic 5-fluorouracil and two sesquiterpenes, nerolidol and valencene on the proliferation of intestinal cancer cells and to find out the influence of sesquiterpenes on antiproliferative effect of 5-fluorouracil. Cancer cell line SW-620 derived from the colorectal metastatic carcinoma was used for our experiments. Neutral red uptake tests were used to measure the number of viable cells. The obtained results showed, that the inhibition of proliferation of cells SW-620 by 5-fluorouracil was concentration and time dependent. Trans-nerolidol showed antiproliferative effect even in low concentrations, while valencene...
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