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Development of the circadian system after systemic potentiation of GABAergic transmission in early ontogenesis
Dušek, Jakub ; Bendová, Zdeňka (advisor) ; Mareš, Pavel (referee)
The circadian system is the evolutionary response of organisms to repetitive geophysical conditions and allows organisms to devote their energy to solving sudden changes. Although the circadian system developed to help organisms survive and thrive in dynamic conditions, system itself is sensitive to external changes. During critical developmental period of the mammalian CNS, the neonatal period, the circadian systém is significantly vulnerable. Benzodiazepines, pharmaceuticals widely prescribed for half a century, interfere with GABAergic transmission, which is critical type of signaling for the functioning of the circadian systém. The purpose of this thesis is to determine whether and how the development and functioning of the circadian system is altered after administration of a drug from the benzodiazepine class, clonazepam, during the critical developmental period. This thesis examines changes in the expression profile of selected genes in the hippocampus, olfactory bulb and frontal cortex of two ontogenetic stages of rats. Results of this work suggest that benzodiazepines administred in the neonatal period disrupt the development of the circadian system and that these changes, particularly in the hippocampus, persist for certain time. Key words: circadian system; circadian rhythms;...
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Calcium homeostasis and modulation of nociceptive synaptic transmission
Sojka, David
This study was designed to improve our knowledge regarding mechanisms of nociceptive signaling at spinal cord level. One of the forms of spinal cord synaptic transmission modulation is central sensitization, a manifestation of synaptic plasticity at spinal cord level, which was found to be present at many chronic pain syndromes. This study deals mainly with a development of calcium imaging technique with a final goal to study mechanisms of central sensitization in vitro on population of dorsal horn neurons. We have analyzed synaptically evoked intracellular Ca changes as a result of dorsal root stimulation in a superficial dorsal horn area in spinal cord slices and found two types of Ca responses: one synchronized with electrical stimulation and a second one, delayed response due to Ca release from internal stores. The delayed Ca release was not previously shown to be present in these neurons and it was not dependent on activation of ionotropic glutamatergic receptors, suggesting involvement of metabotropic receptor pathway. The presence of this delayed type of Ca response could have a significant role in the induction of some types of chronic pain syndromes, since intracellular calcium increase is thought to be a key trigger point in spinal cord neurons sensitization. An important role in neuronal calcium...
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Calcium homeostasis and modulation of nociceptive synaptic transmission
Sojka, David
This study was designed to improve our knowledge regarding mechanisms of nociceptive signaling at spinal cord level. One of the forms of spinal cord synaptic transmission modulation is central sensitization, a manifestation of synaptic plasticity at spinal cord level, which was found to be present at many chronic pain syndromes. This study deals mainly with a development of calcium imaging technique with a final goal to study mechanisms of central sensitization in vitro on population of dorsal horn neurons. We have analyzed synaptically evoked intracellular Ca changes as a result of dorsal root stimulation in a superficial dorsal horn area in spinal cord slices and found two types of Ca responses: one synchronized with electrical stimulation and a second one, delayed response due to Ca release from internal stores. The delayed Ca release was not previously shown to be present in these neurons and it was not dependent on activation of ionotropic glutamatergic receptors, suggesting involvement of metabotropic receptor pathway. The presence of this delayed type of Ca response could have a significant role in the induction of some types of chronic pain syndromes, since intracellular calcium increase is thought to be a key trigger point in spinal cord neurons sensitization. An important role in neuronal calcium...
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