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Previous issue date: 2015-02-13 === Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES === Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq === Funda??o de Amparo ? Pesquisa do Estado do Rio Grande do Sul - FAPERGS === Neonatal exposure to lipopolysaccharides (LPS) generates a stressful stimulus capable of affecting the development of important systems, which causes lasting behavioral and neuroendocrine alterations. The aim of this study is to evaluate the response to an inflammatory stimulus in Balb/c mice exposed to LPS-induced neonatal stress at different ages and genders. Mice underwent intraperitonial injections on postnatal days 3 and 10 with either LPS (100ug/Kg) or saline solution. After 21 or 60 days of age, either saline solution was injected or an inflammatory stimulus was induced by the injection of 1% carrageenan. Inflammatory cytokines, reactive oxygen species and NETs production were measured in the peritoneal lavage. Our findings indicate that LPS-induced neonatal stress can reduce inflammatory cytokines in young animals, males and females. In adults, however, only females showed the same response pattern. In nLPS group, an increase in NETs production was observed in animals that were 60-days-old when compared to 21-days-old in both genders, which indicates an effect of neonatal stress on the ontogeny of NETs formation. The production of ROS was not affected by neonatal stress, even though an increased production was found among adults regardless of neonatal intervention. The results shown here indicate that LPS-induced neonatal stress can alter cytokine production in response to inflammatory stimuli at different ages, in a gender dependent way. Moreover, it seems like the formation of NETs throughout life is also influenced by alterations undergone during the neonatal period. === A exposi??o neonatal ao lipopolissacar?deo (LPS) gera um estimulo estressor capaz de afetar o desenvolvimento de importantes sistemas, dando origem a altera??es comportamentais e neuroend?crinas duradoras. O objetivo desta disserta??o ? avaliar a resposta a um est?mulo inflamat?rio em camundongos Balb/c submetidos ? estresse neonatal por LPS em diferentes idades e sexos. Os camundongos receberam, no 3? e 10? dias de vida, inje??o i.p. de LPS (100?g /Kg) ou solu??o salina. Ap?s 21 ou 60 dias de vida, os mesmos foram submetidos ? inje??o de solu??o salina ou a um est?mulo inflamat?rio atrav?s da inje??o de carragenina 1%. Foram mensurados no lavado peritoneal citocinas inflamat?rias, esp?cies reativas de oxig?nio e produ??o de Redes Extracelulares de Neutr?filos (NETs). Os resultados encontrados demonstram que o estresse neonatal por LPS diminui a libera??o de citocinas inflamat?rias nos animais jovens machos e f?meas. J? nos adultos, somente as f?meas apresentaram a mesma resposta. Foi encontrado um aumento na produ??o de NETs nos animais do grupo nLPS com 60 dias quando comparado com animais nLPS com 21 dias, em ambos os sexos, indicando um efeito do estresse neonatal sobre a ontogenia da forma??o de NETs. A produ??o de ROS n?o sofreu influ?ncia do estresse neonatal, por?m foi encontrada uma maior produ??o na idade adulta, independente da interven??o neonatal. Os resultados do presente estudo indicam que o estresse neonatal por LPS altera a produ??o de citocinas em resposta a um est?mulo inflamat?rio em diferentes idades, em um efeito dependente do sexo. Al?m disso, parece que a forma??o de NETs ao longo da vida tamb?m ? influenciada pelas altera??es no per?odo neonatal.
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