Papel do óxido nítrico no comportamento tipo-depressão induzido por LPS
Ano de defesa: | 2013 |
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Autor(a) principal: | |
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Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Não Informado pela instituição
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Programa de Pós-Graduação: |
Não Informado pela instituição
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Departamento: |
Não Informado pela instituição
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País: |
Não Informado pela instituição
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Palavras-chave em Português: | |
Link de acesso: | http://www.repositorio.ufc.br/handle/riufc/23921 |
Resumo: | Psychiatric disorders, including depression, are among the leading causes of disability in the world. Thus, research on new pathways involved in the pathophysiology of this mental disorder that allows the discovery of new targets for the treatment of this disorder has been extensively studied. Nitric oxide (NO) and its enzymatic nitric oxide synthase (NOS) synthetase have been associated with depression and other affective disorders. In this context, the effect of pre-treatment of drugs that modulate the NO pathway in animals submitted to immunological challenge was determined by the systemic administration of LPS (0.5 mg / kg, ip). For both behaviors related to depression, pre-pulse inhibition (PPI) and locomotor activity, 24 h after endotoxin administration, respectively, were the key points for the development of depressive and neurochemical behaviors through evaluation of TBARS, nitrite and GSH in the cerebral areas (prefrontal cortex - CPF, hippocampus - HC and striatum - CE) were evaluated. LPS-treated animals, as well as those pretreated with L-ariginine prior to LPS, significantly increased the time of immobility in forced swimming compared to controls. A significant reduction in the immobility time of animals pretreated with aminoguanidine was observed when compared to the animals in the control and LPS groups. Remarkably, animals pretreated with sildenafil and L-NAME showed a significant decrease in immobility time when compared to the group receiving only LPS. The results showed that 24 hours after LPS administration, the locomotor activity assessed through the number of crosses in the open field, remained unchanged, with only a significant increase in animals treated with imipramine. A significant decrease in PPI levels was observed 24 h after administration of LPS at the pre-pulse intensities of 70, 75 and 80 dB relative to the control animals. Administration of all other drugs (imipramine, L-arginine, sildenafil, L-NAME and aminoguanidine) was able to prevent the reduction of PPI levels caused after systemic administration of LPS. GSH levels decreased in all brain areas studied, ie, prefrontal cortex, hippocampus and striatum, of LPS treated animals compared to controls. This reduction was maintained by pretreatment with L-arginine in the prefrontal cortex compared to LPS and controlled and prevented by pretreatment with imipramine, L-arginine, sildenafil, L-NAME, and aminoguanidine drugs. In the evaluation of lipid peroxidation after LPS administration, a significant increase in this parameter was evidenced. Administration of imipramine maintained increased levels of TBARS in the prefrontal cortex and striatum compared to control animals, but reduced this parameter when compared to LPS-treated animals. Administration of L-arginine, sildenafil, L-NAME and aminoguanidine reduced levels of lipid peroxidation when compared to LPS-treated animals in all brain areas studied. The pre-administration of imipramine, 1-arginine and aminoguanidine was able to prevent the increase of BDNF levels caused by the systemic administration of LPS. On the other hand, analyzes of BDNF levels 24 h after administration of LPS from animals pretreated with sildenafil and L-NAME did not demonstrate significant changes. An increase in IL-1β content was observed 24 h after administration of LPS in the prefrontal cortex, hippocampus and striatum, all drugs were able to prevent such changes in the hippocampus and striatum. Nitric oxide (NO) plays an important neuromodulatory role in the central nervous system. Any pharmacological manipulation of the NO pathway can be considered as a novel therapeutic approach for the treatment of CNS disorders, more so for mental depression (Heiberg et al., 2002) (1) (1) (1) (1). |
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Papel do óxido nítrico no comportamento tipo-depressão induzido por LPSThe role of nitric oxide in LPS-induced depression-type behaviorOxído NítricoDepressãoEstresse OxidativoReceptores de LipopolissacarídeosPsychiatric disorders, including depression, are among the leading causes of disability in the world. Thus, research on new pathways involved in the pathophysiology of this mental disorder that allows the discovery of new targets for the treatment of this disorder has been extensively studied. Nitric oxide (NO) and its enzymatic nitric oxide synthase (NOS) synthetase have been associated with depression and other affective disorders. In this context, the effect of pre-treatment of drugs that modulate the NO pathway in animals submitted to immunological challenge was determined by the systemic administration of LPS (0.5 mg / kg, ip). For both behaviors related to depression, pre-pulse inhibition (PPI) and locomotor activity, 24 h after endotoxin administration, respectively, were the key points for the development of depressive and neurochemical behaviors through evaluation of TBARS, nitrite and GSH in the cerebral areas (prefrontal cortex - CPF, hippocampus - HC and striatum - CE) were evaluated. LPS-treated animals, as well as those pretreated with L-ariginine prior to LPS, significantly increased the time of immobility in forced swimming compared to controls. A significant reduction in the immobility time of animals pretreated with aminoguanidine was observed when compared to the animals in the control and LPS groups. Remarkably, animals pretreated with sildenafil and L-NAME showed a significant decrease in immobility time when compared to the group receiving only LPS. The results showed that 24 hours after LPS administration, the locomotor activity assessed through the number of crosses in the open field, remained unchanged, with only a significant increase in animals treated with imipramine. A significant decrease in PPI levels was observed 24 h after administration of LPS at the pre-pulse intensities of 70, 75 and 80 dB relative to the control animals. Administration of all other drugs (imipramine, L-arginine, sildenafil, L-NAME and aminoguanidine) was able to prevent the reduction of PPI levels caused after systemic administration of LPS. GSH levels decreased in all brain areas studied, ie, prefrontal cortex, hippocampus and striatum, of LPS treated animals compared to controls. This reduction was maintained by pretreatment with L-arginine in the prefrontal cortex compared to LPS and controlled and prevented by pretreatment with imipramine, L-arginine, sildenafil, L-NAME, and aminoguanidine drugs. In the evaluation of lipid peroxidation after LPS administration, a significant increase in this parameter was evidenced. Administration of imipramine maintained increased levels of TBARS in the prefrontal cortex and striatum compared to control animals, but reduced this parameter when compared to LPS-treated animals. Administration of L-arginine, sildenafil, L-NAME and aminoguanidine reduced levels of lipid peroxidation when compared to LPS-treated animals in all brain areas studied. The pre-administration of imipramine, 1-arginine and aminoguanidine was able to prevent the increase of BDNF levels caused by the systemic administration of LPS. On the other hand, analyzes of BDNF levels 24 h after administration of LPS from animals pretreated with sildenafil and L-NAME did not demonstrate significant changes. An increase in IL-1β content was observed 24 h after administration of LPS in the prefrontal cortex, hippocampus and striatum, all drugs were able to prevent such changes in the hippocampus and striatum. Nitric oxide (NO) plays an important neuromodulatory role in the central nervous system. Any pharmacological manipulation of the NO pathway can be considered as a novel therapeutic approach for the treatment of CNS disorders, more so for mental depression (Heiberg et al., 2002) (1) (1) (1) (1).Os transtornos psiquiátricos, dentre eles a depressão, estão entre as principais causas de incapacidade no mundo. Desta forma, pesquisas a respeito de novas vias envolvidas na fisiopatologia deste transtorno mental que possibilitem a descoberta de novos alvos para o tratamento deste transtorno têm sido amplamente estudados. O óxido nítrico (NO) e a sua enzima de síntese óxido nítrico sintase (NOS) vem sendo relacionados com a depressão e outros transtornos afetivos. Neste contexto buscou-se determinar o efeito do pré-tratamento de drogas que modulam a via do NO em animais submetidos ao desafio imune pela administração sistêmica de LPS (0,5 mg / kg, ip). Para tanto os comportamentos relacionados à depressão, inibição pré-pulso (PPI) e atividade locomotora, 24 h após a administração da endotoxina, respectivamente, ponto de tempo chave para o desenvolvimento de comportamentos tipo depressivo, e neuroquímicas através da avaliação dos níveis de TBARS, Nitrito e GSH nas áreas cerebrais (córtex pré-frontal - CPF, hipocampo - HC e corpo estriado - CE) foram avaliados. Os animais tratados com LPS, bem como os pré-tratados com L-ariginina antes do LPS aumentaram significativamente o tempo de imobilidade no nado forçado em comparação com os controles. Observou-se uma redução significativa no tempo de imobilidade dos animais pré-tratados com aminoguanidina quando em comparação com os animais do grupo controle e LPS. Notavelmente os animais pré-tratados com sildenafil e L-NAME apresentaram uma diminuição significativa do tempo de imobilidade quando comparado ao grupo que recebeu apenas LPS. O resultados mostraram que 24 horas pós a administração de LPS, a atividade locomotora avaliada através do número de cruzamentos no campo aberto, manteve-se inalterada, apenas havendo aumento significativo nos animais tratados com imipramina. Observou-se uma diminuição significativa nos níveis de PPI 24 h após a administração de LPS nas intensidades de pré-pulso de 70, 75 e 80 dB em relação aos animais controle. A administração de todas as outras drogas (imipramina, L-arginina, sildenafil, L-NAME e aminoguanidina), foi capaz de prevenir a redução dos níveis de PPI causada após a administração sistêmica do LPS. Os níveis de GSH diminuiram em todas as áreas cerebrais estudadas, ou seja, córtex pré-frontal, hipocampo e corpo estriado, de animais tratados com LPS quando comparados aos controles. Esta redução foi mantida pelo pré-tratamento com L-arginina no córtex pré-frontal em comparação ao LPS e controle e prevenida pelo pré-tratamento com as drogas imipramina, L-arginina, sildenafil, L-NAME e aminoguanidina. Na avaliação da peroxidação lipídica após a administração do LPS foi evidenciado aumento significativo neste parâmetro. A administração da imipramina manteve o aumento nos níveis de TBARS no córtex pré-frontal e corpo estriado em relação aos animais controle, mas reduziu este parâmetro quando comparado aos animais tratados com LPS. A administração da L-arginina, sildenafil, L-NAME e aminoguanidina reduziu os nível de peroxidação lipídica quando comparado aos animais tratados com LPS em todas as áreas cerebrais estudadas. A pré-administração da imipramina, l-arginina e aminoguanidina foram capazes de prevenir o aumento dos níveis de BDNF causado pela administração sistêmica do LPS. Por outro lado, as análises dos níveis de BDNF 24 h após a administração de LPS dos animais pré-tratados com sildenafil e L-NAME, não demonstraram alterações sisgnificativas. Observou-se um aumento no conteúdo de IL-1β 24 h após a administração de LPS no córtex pré-frontal, hipocampo e corpo estriado, todas as drogas foram capazes de prevenir essas alterações no hipocampo e corpo estriado. O óxido nítrico (NO) desempenha um papel significativo neuromodulador no sistema nervoso central. Qualquer manipulação farmacológica da via de NO pode ser considerado como uma nova abordagem terapêutica para o tratamento de distúrbios do SNC, mais ainda para a depressão mental(Heiberg et al., 2002)(1)(1)(1)(1).Gaspar, Danielle MacêdoTomaz, Viviane de Sousa2017-07-10T14:14:26Z2017-07-10T14:14:26Z2013-08-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfTOMAZ, V. S. Papel do óxido nítrico no comportamento tipo-depressão induzido por LPS. 2013. 75 f. Dissertação (Mestrado em Microbiologia Médica) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2013.http://www.repositorio.ufc.br/handle/riufc/23921porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2021-02-09T19:52:58Zoai:repositorio.ufc.br:riufc/23921Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T19:03:41.254185Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false |
dc.title.none.fl_str_mv |
Papel do óxido nítrico no comportamento tipo-depressão induzido por LPS The role of nitric oxide in LPS-induced depression-type behavior |
title |
Papel do óxido nítrico no comportamento tipo-depressão induzido por LPS |
spellingShingle |
Papel do óxido nítrico no comportamento tipo-depressão induzido por LPS Tomaz, Viviane de Sousa Oxído Nítrico Depressão Estresse Oxidativo Receptores de Lipopolissacarídeos |
title_short |
Papel do óxido nítrico no comportamento tipo-depressão induzido por LPS |
title_full |
Papel do óxido nítrico no comportamento tipo-depressão induzido por LPS |
title_fullStr |
Papel do óxido nítrico no comportamento tipo-depressão induzido por LPS |
title_full_unstemmed |
Papel do óxido nítrico no comportamento tipo-depressão induzido por LPS |
title_sort |
Papel do óxido nítrico no comportamento tipo-depressão induzido por LPS |
author |
Tomaz, Viviane de Sousa |
author_facet |
Tomaz, Viviane de Sousa |
author_role |
author |
dc.contributor.none.fl_str_mv |
Gaspar, Danielle Macêdo |
dc.contributor.author.fl_str_mv |
Tomaz, Viviane de Sousa |
dc.subject.por.fl_str_mv |
Oxído Nítrico Depressão Estresse Oxidativo Receptores de Lipopolissacarídeos |
topic |
Oxído Nítrico Depressão Estresse Oxidativo Receptores de Lipopolissacarídeos |
description |
Psychiatric disorders, including depression, are among the leading causes of disability in the world. Thus, research on new pathways involved in the pathophysiology of this mental disorder that allows the discovery of new targets for the treatment of this disorder has been extensively studied. Nitric oxide (NO) and its enzymatic nitric oxide synthase (NOS) synthetase have been associated with depression and other affective disorders. In this context, the effect of pre-treatment of drugs that modulate the NO pathway in animals submitted to immunological challenge was determined by the systemic administration of LPS (0.5 mg / kg, ip). For both behaviors related to depression, pre-pulse inhibition (PPI) and locomotor activity, 24 h after endotoxin administration, respectively, were the key points for the development of depressive and neurochemical behaviors through evaluation of TBARS, nitrite and GSH in the cerebral areas (prefrontal cortex - CPF, hippocampus - HC and striatum - CE) were evaluated. LPS-treated animals, as well as those pretreated with L-ariginine prior to LPS, significantly increased the time of immobility in forced swimming compared to controls. A significant reduction in the immobility time of animals pretreated with aminoguanidine was observed when compared to the animals in the control and LPS groups. Remarkably, animals pretreated with sildenafil and L-NAME showed a significant decrease in immobility time when compared to the group receiving only LPS. The results showed that 24 hours after LPS administration, the locomotor activity assessed through the number of crosses in the open field, remained unchanged, with only a significant increase in animals treated with imipramine. A significant decrease in PPI levels was observed 24 h after administration of LPS at the pre-pulse intensities of 70, 75 and 80 dB relative to the control animals. Administration of all other drugs (imipramine, L-arginine, sildenafil, L-NAME and aminoguanidine) was able to prevent the reduction of PPI levels caused after systemic administration of LPS. GSH levels decreased in all brain areas studied, ie, prefrontal cortex, hippocampus and striatum, of LPS treated animals compared to controls. This reduction was maintained by pretreatment with L-arginine in the prefrontal cortex compared to LPS and controlled and prevented by pretreatment with imipramine, L-arginine, sildenafil, L-NAME, and aminoguanidine drugs. In the evaluation of lipid peroxidation after LPS administration, a significant increase in this parameter was evidenced. Administration of imipramine maintained increased levels of TBARS in the prefrontal cortex and striatum compared to control animals, but reduced this parameter when compared to LPS-treated animals. Administration of L-arginine, sildenafil, L-NAME and aminoguanidine reduced levels of lipid peroxidation when compared to LPS-treated animals in all brain areas studied. The pre-administration of imipramine, 1-arginine and aminoguanidine was able to prevent the increase of BDNF levels caused by the systemic administration of LPS. On the other hand, analyzes of BDNF levels 24 h after administration of LPS from animals pretreated with sildenafil and L-NAME did not demonstrate significant changes. An increase in IL-1β content was observed 24 h after administration of LPS in the prefrontal cortex, hippocampus and striatum, all drugs were able to prevent such changes in the hippocampus and striatum. Nitric oxide (NO) plays an important neuromodulatory role in the central nervous system. Any pharmacological manipulation of the NO pathway can be considered as a novel therapeutic approach for the treatment of CNS disorders, more so for mental depression (Heiberg et al., 2002) (1) (1) (1) (1). |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-08-31 2017-07-10T14:14:26Z 2017-07-10T14:14:26Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
TOMAZ, V. S. Papel do óxido nítrico no comportamento tipo-depressão induzido por LPS. 2013. 75 f. Dissertação (Mestrado em Microbiologia Médica) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2013. http://www.repositorio.ufc.br/handle/riufc/23921 |
identifier_str_mv |
TOMAZ, V. S. Papel do óxido nítrico no comportamento tipo-depressão induzido por LPS. 2013. 75 f. Dissertação (Mestrado em Microbiologia Médica) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2013. |
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http://www.repositorio.ufc.br/handle/riufc/23921 |
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openAccess |
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Universidade Federal do Ceará (UFC) |
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Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC) |
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