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The role of nociceptive synaptic transmission modulation
Heleš, Mário ; Paleček, Jiří (advisor) ; Rokyta, Richard (referee) ; Krůšek, Jan (referee)
Pain represents a major symptom in a multitude of medical conditions and can often become the main negative factor in a patient's low quality of life. The complex issue of pain management is further underscored by the reduced efficacy of conventional analgesics in conditions such as neuropathic pain. Neuropathic pain, unlike acute nociceptive pain, originates from damage to the peripheral or central nervous system and often develops into chronic pain syndrome. Most analgesics available today provide only limited and unsatisfactory analgesia in chronic neuropathic pain and are often associated with severe adverse effects. Modulation of nociceptive transmission in spinal cord dorsal horn (SCDH) stands out in recent research as a pivotal mechanism, especially in chronic pain development and maintenance. The major aim of this doctoral thesis was to investigate how pain-associated processes interfere with opioid-induced analgesia, with the main focus on the interaction between chemokine (C-C motif) ligand 2 (CCL2), transient receptor potential vanilloid type 1 (TRPV1), and μ-opioid receptor (MOR). To achieve a better insight into opioid signaling in SCDH we studied the following issues: (I.) How does CCL2 modulate MOR-mediated effects on nociceptive synaptic transmission in SCDH neurons and in vivo...
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The role of TRP ion channels in rheumatoid arthritis pain
Havrilčáková, Gabriela ; Zímová, Lucie (advisor) ; Heleš, Mário (referee)
Rheumatoid arthritis is a disease that affects many people across the world. It is a chronic autoimune disease causing inflammation in joints. The inflammation affects joint lining and causes gradual damage to the joint cartilage. Main symptoms are swelling and pain, The perception of pain is closely related to a group of TRP receptors expressed on sensory neurons. The state of inflammation in the affected joints also has a significant influence on the pain accopanying rheumatoid arthritis, in which participate the cells of the joint lining - synovial fibroblasts. They express a subset of TRP receptors that play a key role in the pathophysiology of arthritis development as well. In relation to pain and inflammation, the most studied TRP receptors are TRPV1 and TRPA1. This bachelor thesis describes the findings on these two receptors in relation to pain in rheumatoid arthritis. However, it also describes the TRPC5 receptor, whose inhibiton has only recently been shown in a mouse model to leads to exacerbation of symptoms. The results discussed in this bachelor's thesis show, that pharmacological modulation of the activity of TRP receptors is a promising way of possible future treatment of rheumatoid arthritis, including its main symptom - pain. Key words: rheumatoid arthritis, transient receptor...
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Glial cells in central nervous system pathology: the role of Wnt signaling
Bronišová, Denisa ; Kriška, Ján (advisor) ; Heleš, Mário (referee)
Wnt signaling plays an important role in regulating cell growth, differentiation, or movement. This represents a potential in the treatment of pathologies in which the proliferation or differentiation of new cells could be key to the regeneration and mitigation of the consequences of the disease. Glial cells are more than just a glue for neurons, and they have important roles in pathologies in maintaining cell metabolism and survival, and brain functioning in general. The aim of this bachelor thesis is to provide a literature review of the roles of Wnt signaling in glial cells in the healthy brain, but especially in central nervous system (CNS) pathologies. The work provides an overview of the main types of glial cells in the CNS, a description of three Wnt signaling pathways, and focuses in detail on selected CNS pathologies and the role and changes of Wnt signaling that occur in these pathologies. Further research utilizing the potential of Wnt signaling in glial cells might lead to the development of novel therapies that could change the fate of patients with CNS diseases.
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The role of Akt / protein kinase B in healthy and hypertrophied heart
Heleš, Mário ; Žurmanová, Jitka (advisor) ; Hrdlička, Jaroslav (referee)
Protein kinase B, or Akt kinase is expressed in almost all tissues. Two main isoforms in heart are Akt1 and Akt2, which are responsible for regulation of metabolism, growth and survival of cardiomyocytes. Akt kinase is among other pathways stimulated by insulin receptor and mechanoreceptor cascades and its main targets are mTORC1, AMPK and GSK- 3β. Akt kinase is activated in presence of chronic hemodynamic overload of heart. In dependence of intensity and duration of overload, Akt participate in triggering of either adaptive, fully reversible hypertrophy or detrimental irreversible form of hypertrophy, which causes impairment of pumping function of heart and can lead to heart failure. Many more factors with complex interactions participate in cardiac hypertrophy beside Akt kinase. Key words: heart, hypertrophy, Akt/protein kinase B, cardiac remodeling, insulin- like growth factor
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Neurosteroid effects on neuronal network activity in vitro.
Strnadová, Lenka ; Smejkalová, Terézia (advisor) ; Heleš, Mário (referee)
GABA receptors type A (GABAAR) are ligand-gated ion channels permeable for chloride anions. In the mammalian brain they mediate most of the inhibitory transmission. Moreover, the dysfunctions of the GABA-mediated system result in many neurological disorders, including epilepsy, anxiety and depression. Neurosteroids are cholesterol metabolites interacting with a variety of membrane receptors and have a direct effect on neuronal excitability. The neurosteroids allo-pregnanolone (allo-PA) and pregnanolone (PA) are potent positive modulators of the GABAAR. The goal of this work is to establish a newly constructed application system and a calcium imaging method using the GCaMP sensor to examine the effects of PA on the activity of primary hippocampal cultures. In this work we validate the application system and test the GCaMP calcium sensor in vitro. Application of PA inhibited the spontaneous calcium peaks, which agrees with its known actions on the GABAAR. We discovered that the neurosteroid inhibitory effect on the neuronal network activity changes after repeated applications. The results suggest that there might be some compensatory actions on the GABAAR level during prolonged or repeated exposition to PA. Key words: GABAAR; neurosteroid; pregnanolone; allopregnanolone; calcium; GCaMP; inhibition
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Relationship between the renin-angiotensin-aldosterone system and the heart and its influence during 5°C cold acclimation.
Hlaváčová, Diana ; Horníková, Daniela (advisor) ; Heleš, Mário (referee)
Heart as one of the life-important organs is influenced by many ongoing processes in organism. Even the smallest molecular changes can importantly influence heart's physiology and activity. Last years, there were many studies concentrating on clarification of renin-angiotensin- aldosteron system (RAAS) and its influence on heart and kidneys. Cardiovascular diseases are usually caused by changes in RAAS and that is the reason why more and more experts are examining the extent to which diseases can be prevented and heart function improved. Ambient temperature is one of the factors that greatly affects the RAAS and the heart. In this thesis I tried to summarize current knowledge about RAAS and its effects on organism, focusing on influencing the physiology of the heart. While ambient temperature has significant effect on the RAAS and the heart, this thesis points to the knowledge associated with cold acclimation at 5 řC. Key words: renin-angiotensin-aldosteron system, heart, cold, hypertension, adrenergic receptors, natriuretic peptides
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The role of creatine and branched chain amino acids supplementation in muscle physiology and its possible clinical use
Zacpálek, Pavel ; Žurmanová, Jitka (advisor) ; Heleš, Mário (referee)
(in English) Creatine kinase system could be considered the energetic frontline of a cell. It creates and maintains a cellular energy storage and at the same time enables the very fastest response to a high energy demand. Aims of this thesis were to thoroughly describe the creatine kinase system, its role in the energy metabolism and metabolism of creatine molecule itself. As a popular nutritional supplement, there was an emphasis on creatine's impact on the physiology of skeletal muscle and also its higher intake. Furthermore some of the creatine-related disorders were described, as well as research of their treatment. Lastly, the branch-chained amino acids were researched for possible synergic effect with creatine, connection between these two was found through the mTOR signalling pathway.
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