Efeitos da privação de sono paradoxal na resposta ao lipopolissacarídeo bacteriano: aspectos imunológicos, comportamentais e neuroquímicos em camundongos

• Ano de defesa: 2009
• Autor(a) principal: Zager, Adriano [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Comportamento doentio; Sistema imunológico; Lipopolissacarídeos; Sono; Immune system; Lipopolysaccharides
• Link de acesso: https://repositorio.unifesp.br/handle/11600/9406

Sleep is a fundamental biologic phenomenon that is essential for the preservation of human health. Still, the time we send awake is increasing ever more due to intense activities and the social and economic pressure exerted by society. Except for the well documented physiologic consequences of sleep deprivation (SD), the interaction sleep has with the immune system as well as the association of SD to specific immunologic stimuli remain inconclusive. The aim of the current study was thus to investigate the effects of paradoxical sleep deprivation (PSD) in the immune and behavioral response to lipopolysaccharide (LPS) of E. coli, a powerful immunological activator, and alterations in neurotransmission and expression of inflammatory proteins within the central nervous system. For such, C57BL/6J mice were submitted to PSD for 72 hours while controls remained in their home-cages and maintained a normal sleep regimen. At the end of the PSD period all animals were administered a saline injection or one of the LPS doses and were returned to their respective cages for an interval of 2 hours before the immunologic, behavioral, and neurochemical analysis were performed. Results demonstrated that PSD was capable of causing a reduction of lymphocytes in the bloodstream and within spleen of the animals administered saline, but other lymphocyte migration sites (peritoneum and lymph nodes) were not affected indicating that such effects of PSD are not due to alteration of cellular migration. No significant difference was encountered in animals administered with whichever dose of LPS. PSD was also found to be capable of increasing susceptibility to the behavioral effects induced by LPS, particularly in the open field test. Furthermore, the alterations in the sleep pattern that were caused by LPS inhibited paradoxical sleep rebound, a phenomenon that occurs in sleep deprived animals. Such behavioral alterations reflect changes in dopaminergic neurotransmission within the striatum and in the expression of cyclooxigenase-2 protein within the cortex of these animals. We can thus conclude that sleep exerts a fundamental role as a response modulator to an immune stimulus by altering the immune and behavioral response. Our study provides new findings about the physiological basis of the association between sleep and the immune system.