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Modulation of synaptic transmission in the development of painful states
Slepička, Jakub ; Paleček, Jiří (advisor) ; Hejnová, Lucie (referee)
My thesis introduces the topic of nociceptive signalisation and processes involved in the formation and spreading of neuropathic pain. This study focuses on the mechanisms of nociceptive synaptic transmission mechanisms in the level of spinal dorsal horn and its modulation by paclitaxel, a chemotherapeutic drug inducing neuropathic changes. The attention is put especially on the possibility of glial activity participation in paclitaxel side effects. This idea stems from the existing hypothesis of the functional connection between TLR4 and TRPV1 receptor activity. TRPV1 is well known for its participation in chemical, thermal and nociceptive sensory transmission. Minocycline antibiotic is considered as an inhibitor of microglial activation therefore it was used for blocking neuroinflammation. The experimental part is comparing an impact of substances applied to the model of tachyphylaxis used for monitoring of nociceptive transmission changes according to decreasing activity of TRPV1 receptors. Electrophysiological recording of miniature excitatory postsynaptic currents from neurons in the Rexed laminae I. and II. of spinal dorsal horn was used. The results of my measurements show that minocycline is able to suppress acute effects of paclitaxel application in vitro if the spinal slice is incubated...
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Role of M4 muscarinic receptors in the central nervous system
Křížová, Monika ; Mysliveček, Jaromír (advisor) ; Slepička, Jakub (referee)
Muscarinic receptors type 4 are one of the five subtypes of muscarinic receptors, that are members of cholinergic receptors family, together with nicotinic receptors. An acetylcholine binding on the receptor triggers the receptor activation and the signal transmission into the cell by G-proteins located on plasmatic membrane, in the case of muscarinic receptors type 4 by Gi/o proteins. The M4 receptors are, just like other subtypes on muscarinic receptors, located in central and peripheral nervous system. In the central nervous system, they are mostly located in striatum and hippocampus. The M4 receptors have a whole range of regulative functions, the most significant one is most likely the regulation of a locomotion in striatum by the dopaminergic system. The muscarinic receptors type 4 are involved in many behavioural and cognitive processes and are therefore studied as potential drug target for the treatment of mental disorders. Key words: muscarinic receptors, M4 muscarinic receptors, GPCRs, cholinergic system, central nervous system
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Role of M4 muscarinic receptors in the central nervous system
Křížová, Monika ; Mysliveček, Jaromír (advisor) ; Slepička, Jakub (referee)
Muscarinic receptors type 4 are one of the five subtypes of muscarinic receptors, that are members of cholinergic receptors family, together with nicotinic receptors. An acetylcholine binding on the receptor triggers the receptor activation and the signal transmission into the cell by G-proteins located on plasmatic membrane, in the case of muscarinic receptors type 4 by Gi/o proteins. The M4 receptors are, just like other subtypes on muscarinic receptors, located in central and peripheral nervous system. In the central nervous system, they are mostly located in striatum and hippocampus. The M4 receptors have a whole range of regulative functions, the most significant one is most likely the regulation of a locomotion in striatum by the dopaminergic system. The muscarinic receptors type 4 are involved in many behavioural and cognitive processes and are therefore studied as potential drug target for the treatment of mental disorders. Key words: muscarinic receptors, M4 muscarinic receptors, GPCRs, cholinergic system, central nervous system
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Modulation of synaptic transmission in the development of painful states
Slepička, Jakub ; Paleček, Jiří (advisor) ; Hejnová, Lucie (referee)
My thesis introduces the topic of nociceptive signalisation and processes involved in the formation and spreading of neuropathic pain. This study focuses on the mechanisms of nociceptive synaptic transmission mechanisms in the level of spinal dorsal horn and its modulation by paclitaxel, a chemotherapeutic drug inducing neuropathic changes. The attention is put especially on the possibility of glial activity participation in paclitaxel side effects. This idea stems from the existing hypothesis of the functional connection between TLR4 and TRPV1 receptor activity. TRPV1 is well known for its participation in chemical, thermal and nociceptive sensory transmission. Minocycline antibiotic is considered as an inhibitor of microglial activation therefore it was used for blocking neuroinflammation. The experimental part is comparing an impact of substances applied to the model of tachyphylaxis used for monitoring of nociceptive transmission changes according to decreasing activity of TRPV1 receptors. Electrophysiological recording of miniature excitatory postsynaptic currents from neurons in the Rexed laminae I. and II. of spinal dorsal horn was used. The results of my measurements show that minocycline is able to suppress acute effects of paclitaxel application in vitro if the spinal slice is incubated...
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The role of TLR-4 receptors for modulation of nociceptive signalling.
Slepička, Jakub ; Paleček, Jiří (advisor) ; Zímová, Lucie (referee)
The ability to feel pain is subjective, but a crucial factor allowing us to maintain life with minimal body impairment. However, if the pain crosses the physiological signalling function it becomes a life restrictive symptom that is often difficult to treat. Development of pain and its change into pathological chronic symptom and the role of different molecular and cellular mechanisms in this process are best to be studied during its development, nociception. In this work the basic characteristics of nociceptive signalling, with focus on neuropathy, a state originating from nervous system damage is given. The exact mechanisms of neuropathic pain development are not known, which is one of the reasons why these painful states are difficult to treat. Neuroinflammation was lately shown to play an important part in the neuropathy development. In this context a review of Toll-like receptors is given. These receptors have a fundamental role in the innate immunity and their role in the nervous system was documented recently. In this review a focus is given on TLR-4 subtype that was shown to be involved in a modulation of nociceptive signalling. The basic features of this receptor and information about its involvement in neuropathic pain development are given. Studying the role of TLR-4 in different models...
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