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Effects of paradoxical sleep deprivation on the development and progression of experimental metastasis in a model of murine melanoma

Grant number: 12/14525-5
Support type:Scholarships in Brazil - Master
Effective date (Start): November 01, 2012
Effective date (End): July 31, 2014
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Deborah Suchecki
Grantee:Laís de Oliveira Marchioro
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Paradoxical sleep deprivation (PSD) is considered a stressor because it increases glucocorticoids (GC) levels in humans (cortisol) and rodents (corticosterone), by activation of the hypothalamic-pituitary-adrenal (HPA), which can lead to a variety of disorders resulting from prolonged and / or elevated hormone secretion. Some studies show an association between infection and inflammation states and lethargy or drowsiness, while others indicate that sleep-deprived individuals are more susceptible to infections. These data led to interest in studying the interaction between sleep and the immune system. Since prolonged stress is associated with reduced activity of cytotoxic T cells and natural killer (NK) cells, processes such as immune surveillance against tumors and stability mechanisms of genomic somatic mutations may be affected. Thus, the persistent activation of the HPA axis in response to stress, may contribute to development and progression of tumours. The purpose of the present study is to investigate the effects of PSP on the tumour implantation and progression in a murine melanoma model, assessed in different time-points throughout the development of metastasis (in general, 11 days). Variations in immune populations within the spleen and the infiltrating tumor will be evaluated. Thus, C57BL/6 male mice will be inoculated with 1x10(5) cells of B16F10 murine melanoma and, subsequently, submitted to 72 h of PSP, using the modified multiple platform method. Therein, evaluations of metastasis, immune splenic and tumor microenvironment populations, plasma and tissue production of cytokines, as well as the evaluation of plasma corticosterone will be carried out, in addition to tests for functional activity of T cells. (AU)