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Publico-12928j.pdf: 1928961 bytes, checksum: bfccdba529b27f5fabe99133543b72bf (MD5) / O gene Per3 está envolvido na regulação de mecanismos de temporização circadiana. Sua real função ainda não está totalmente elucidada. Algumas hipóteses atuais nos levam a crer que este gene tenha algum papel no mecanismo de sincronização ao estímulo luminoso em ciclos claro/escuro. O principal objetivo deste trabalho foi investigar as possíveis associações entre o gene Per3 e a regulação da ritmicidade circadiana dependente da duração da fotofase. A parte experimental foi dividida em duas etapas: 1. Trabalhamos com camundongos knockout para o gene (Per3-/-) e avaliamos os possíveis mecanismos pelos quais o gene poderia estar envolvido na adaptação e duração da fotofase, expondo esses animais a regimes de claro/escuro diferenciados de forma que houvesse fotofases muito curtas ou longas. 2. Foi feito um experimento em humanos, em duas localidades (Natal e São Paulo) situadas em diferentes latitudes (05°47’S e 23°32’S, respectivamente). O protocolo experimental foi realizado em estações do ano diferentes de forma que pudéssemos mimetizar a variação de fotofase usada em condições laboratoriais. O experimento em humanos foi feito com o intuito de verificar se as inferências feitas a partir do modelo animal eram de alguma forma aplicáveis. Sugerimos a partir dos resultados obtidos na primeira fase do estudo que os animais Per3-/- sejam menos sensíveis ao mascaramento à luz e os resultados da segunda etapa mostram, um atraso nas fases das variáveis circadianas analisadas (início e final da atividade, meia fase de M10 da atividade e meia fase de M6 da temperatura) em Natal, principalmente no grupo de indivíduos do genótipo PER35/5 durante o mês de novembro. De maneira geral, os dados nos camundongos apontam um caminho relacionado com estudos de mascaramento à luz para elucidação da função do gene e os dados em humanos mostram que é possível associá-lo aos ajustes de fase derivados de características específicas do ciclo claro/escuro dados por diferentes latitudes. / Per3 gene is a component of the circadian molecular mechanism. Its function is not completely understood. One of the hypotheses is that Per3 gene may be involved in light synchronization mechanism. The aim of this project was investigate the association between Per3 gene and circadian rhythmicity dependent of the photophase duration in different light/dark cycle regimens. The experimental protocol was divided in two parts: 1. We investigated the possible mechanisms of association between Per3 gene and adaptation/duration of the photophase in Per3-/- mice by exposing the animals to different light/dark cycles with long or short photophases 2. Based on the results of experiment 1, we developed an experiment in humans in order to investigate if the results in mice were someway applicable to our population. Subjects from two locations with different latitudes were selected (Natal and São Paulo) and the experiment was carried out in two different seasons of the year to mimic photophase variation. The first part of our results suggested that Per3 gene is associated with sensitivity of masking by light. In the second part of the study, we found a phase delay in the circadian parameters analyzed (beginning and end of activity, markers of activity (M10) and temperature (M6)) in the PER35/5 group from Natal on November, when compared to the São Paulo group. Our data in mice point out a new hypothesis related to masking effect that may contribute to the understanding of Per3 gene function in the regulation of circadian rhythms and the human data show that it is possible to associate Per3 gene with the phase adjustments derived from specific characteristics of light/dark cycle in different latitudes. / TEDE / BV UNIFESP: Teses e dissertações
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.unifesp.br:11600/9552 |
| Date | 28 September 2011 |
| Creators | Pereira, Danyella Silva [UNIFESP] |
| Contributors | Universidade Federal de São Paulo (UNIFESP), Pedrazzoli, Mario [UNIFESP] |
| Publisher | Universidade Federal de São Paulo (UNIFESP) |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | 240 p. |
| Source | reponame:Repositório Institucional da UNIFESP, instname:Universidade Federal de São Paulo, instacron:UNIFESP |
| Rights | info:eu-repo/semantics/openAccess |
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