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Title: The role of GPR39 in the glutamatergic and gabaergic transmission


The purpose of this doctoral dissertation was to investigate the effect of GPR39 zinc receptor modulation on glutamatergic and gabergic transmission. In this study we used a highly selective GPR39 receptor agonist, TC-G 1008, which showed a fast and prolonged antidepressant effect in a forced swim test in mice. In the experiments we used a scheme of combined administration of TC-G 1008 with selected NMDA, AMPA, GABAA and GABAB receptor ligands. The effects of the treatments were tested in the forced swimming test. At the next stage of the study, the GPR39 agonist was used in animals subjected to a diet with reduced zinc content for a period of 4 or 6 weeks. The behavioural effect of TC-G 1008 was examined in the forced swimming test. Samples of the hippocampus and frontal cortex following chronic agonist administrations and the experimental diet were tested using the Western blot method. The results obtained in this study showed that the antidepressant effect of TC-G 1008 is associated with NMDA and GABAA receptor function. There was no significant relationship between GPR39 and GABAB and AMPA receptors. Chronic administration of TC-G 1008 did not induce adaptive changes in NMDA, GABAA and GABAB receptors. The results showed the dependence of the antidepressant properties of the GPR39 agonist on the amount of zinc in the diet. The effect of diet on PSD95 and KCC2 protein expre ; ssion in response to the GPR39 agonist was also observed. This research expanded knowledge about the properties of TC-G 1008 and showed the dependence of behavioural effects of GPR39 modulation on the function of NMDA and GABAA receptors. The collected data may be the basis for continuing research on GPR39 in the context of glutamatergic and gabergic signaling, and indicate the zinc receptor as a promising target for the development of new antidepressant drugs.

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2 - studia doktoranckie

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Rada Dyscypliny Nauki farmaceutyczne


Młyniec, Katarzyna

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tylko w bibliotece

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Apr 8, 2024

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Jan 21, 2022

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ZB-132237 Apr 8, 2024


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