Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2014. / Made available in DSpace on 2014-08-06T18:02:40Z (GMT). No. of bitstreams: 1
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Previous issue date: 2014 / Abstract : Congenital hypothyroidism can lead to a variety of neurochemical and morphophysiological alterations that may be associated with learning deficits, hypomyelination and delayed development of the central nervous system (CNS). In this study, it has been investigated whether the hormone 3,3',5' -triiodothyronine (reverse T3, rT3) is able to reverse the biochemical changes caused by congenital hypothyroidism in hippocampal slices from 15 day-old rats, as well as the mechanism of action of this hormone. Congenital hypothyroidism was induced by adding 0.05% propylthiouracil (PTU) in the drinking water from gestation day 8 and continually up to lactation day 15. Euthyroid rats, receiving only water during the same period, were used as controls. Control and hypothyroid pups were used at 15 day-old, considering the period of maximum synaptogenesis. Hippocampal slices from controls and hypothyroid pups were incubated for 30 min with or without rT3 (10-9 M). Receptor antagonists (RGD and AP-5), inhibitors or activators of cell signaling pathways of p38, CaMKII, ERK1/2, PKA and PKC (SB239063, KN-93, PD98059, H89 and PMA, respectively), as well as L-type voltage-dependent calcium channel blocker (nifedipine) and intracellular calcium chelator (BAPTA -AM), were used to determine the mechanisms involved in the nongenomic action of rT3 on hippocampal cells. We also analyzed some biochemical markers (aminotransferase activity) and oxidative stress parameters, as well as changes in the uptake of 45Ca++ and [14C]-2-deoxy-D-glucose in the hippocampus of immature rats treated or not with rT3. Results showed that hypothyroidism leads to accumulation of intracellular Ca++ and induces oxidative stress. On the other hand, rT3, previously considered as an inactive metabolite of thyroid hormones (TH), was able to reverse, at least some of the biochemical changes induced by congenital hypothyroidism. In this context, rT3 interacts with the surface ?vß3 integrin receptors activating several signal transduction pathways (PKA, CaMKII, ERK1/2 and p38). These events cause a decrease in 45Ca++ influx, stimulation in [14C]-2-deoxy-D-glucose uptake, as well as reverse the oxidative stress induced by congenital hypothyroidism. Considering that changes in TH levels could be associated with neurodegenerative disorders, depression, anxiety, among others, the understanding of mechanisms of action of these hormones might allow the development of more specific and targeted drugs in controlling several physiopathological disorders of CNS.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufsc.br:123456789/123291 |
| Date | January 2014 |
| Creators | Domingues, Juliana Tonietto |
| Contributors | Universidade Federal de Santa Catarina, Souza, Ariane Zamoner Pacheco de |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | 132 p.| il., grafs., tabs. |
| Source | reponame:Repositório Institucional da UFSC, instname:Universidade Federal de Santa Catarina, instacron:UFSC |
| Rights | info:eu-repo/semantics/openAccess |
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