Estresse prolongado único-emocional induz distúrbio gastrointestinal funcional: um modelo de interação cérebro-intestino
Ano de defesa: | 2022 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
|
Departamento: |
Bioquímica
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/26275 |
Resumo: | Currently, about 90% of the world’s population suffers from some degree of stress, making it an inevitability (WHO). It is known that excessive stress can precipitate psychopathologies, such as depression and anxiety, and alter gastrointestinal functionality and microbiota. Consequently, favoring the development of functional gastrointestinal disorders (FGIDs), which are defined by deregulation in the brain-gut interaction. In this context, animal models of stress become a tool useful to elucidate the mechanisms involved in this interaction. However, most FGIDs models are chronic or have limited validity. Therefore, this study aimed to investigate whether a model of emotional stress induces FGID, through bidirectional braingut interaction mediated by depressive/anxious-like phenotype, intestinal dysfunction, and modulation of intestinal bacterial microbiota in adult male Swiss mice. This study was approved by the UFSM Ethics Committee on the use of animals under number # 1535120320. First, the animals were divided into two groups [Control and Emotional-Single Prolonged Stress (ESPS)], mice in the E-SPS group were subjected to a single sequential exposure to three stressors: immobilization (2h), forced swimming (15min), followed by recovery (15min), and finally exposure to predator odor (3min). After 7 days (incubation period), the animals were evaluated in behavioral tests predictive of depression and anxiety. The parameters, the number of fecal pellets and fecal moisture content (%), were determined. After 24h, samples of stool, blood, and colon tissue were collected for analysis. The results showed depressive- and anxious-like phenotypes in animals subjected to the E-SPS demonstrated in tests predictive of depression (tail suspension test, forced swimming, and splash test) and anxiety (elevated plus maze test), suggesting the brain-gut interaction. E-SPS mice had the intestinal functionality altered, increased intestinal transit, number of fecal pellets and, fecal moisture content, and increased intestinal permeability, associated with a decrease in epithelial junction proteins, significantly Claudin-1. Furthermore, exposure to E-SPS modulated the profile and diversity of the intestinal microbiota of the animals when compared to the non-stressed group. Specifically, a decrease in the relative abundance of the phylum Bacteroidetes, class Bacteroidia, order Bacteroidales, family Muribaculaceae and Prophyromonadaceae, as well as an increase in the phyla Firmicutes and Actinobacteria, order Coriobacteriales, and the Firmicutes/Bacteroidetes ratio and the presence of the genus Mucispirillum. Taken together, the results demonstrated that the E-SPS model induced FGID, through the brain-gut interaction, mediated by behavioral changes, intestinal dysfunction, and modulation of the intestinal bacterial microbiota in male Swiss mice. |
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2022-09-27T17:40:04Z2022-09-27T17:40:04Z2022-08-30http://repositorio.ufsm.br/handle/1/26275Currently, about 90% of the world’s population suffers from some degree of stress, making it an inevitability (WHO). It is known that excessive stress can precipitate psychopathologies, such as depression and anxiety, and alter gastrointestinal functionality and microbiota. Consequently, favoring the development of functional gastrointestinal disorders (FGIDs), which are defined by deregulation in the brain-gut interaction. In this context, animal models of stress become a tool useful to elucidate the mechanisms involved in this interaction. However, most FGIDs models are chronic or have limited validity. Therefore, this study aimed to investigate whether a model of emotional stress induces FGID, through bidirectional braingut interaction mediated by depressive/anxious-like phenotype, intestinal dysfunction, and modulation of intestinal bacterial microbiota in adult male Swiss mice. This study was approved by the UFSM Ethics Committee on the use of animals under number # 1535120320. First, the animals were divided into two groups [Control and Emotional-Single Prolonged Stress (ESPS)], mice in the E-SPS group were subjected to a single sequential exposure to three stressors: immobilization (2h), forced swimming (15min), followed by recovery (15min), and finally exposure to predator odor (3min). After 7 days (incubation period), the animals were evaluated in behavioral tests predictive of depression and anxiety. The parameters, the number of fecal pellets and fecal moisture content (%), were determined. After 24h, samples of stool, blood, and colon tissue were collected for analysis. The results showed depressive- and anxious-like phenotypes in animals subjected to the E-SPS demonstrated in tests predictive of depression (tail suspension test, forced swimming, and splash test) and anxiety (elevated plus maze test), suggesting the brain-gut interaction. E-SPS mice had the intestinal functionality altered, increased intestinal transit, number of fecal pellets and, fecal moisture content, and increased intestinal permeability, associated with a decrease in epithelial junction proteins, significantly Claudin-1. Furthermore, exposure to E-SPS modulated the profile and diversity of the intestinal microbiota of the animals when compared to the non-stressed group. Specifically, a decrease in the relative abundance of the phylum Bacteroidetes, class Bacteroidia, order Bacteroidales, family Muribaculaceae and Prophyromonadaceae, as well as an increase in the phyla Firmicutes and Actinobacteria, order Coriobacteriales, and the Firmicutes/Bacteroidetes ratio and the presence of the genus Mucispirillum. Taken together, the results demonstrated that the E-SPS model induced FGID, through the brain-gut interaction, mediated by behavioral changes, intestinal dysfunction, and modulation of the intestinal bacterial microbiota in male Swiss mice.Atualmente, segundo a Organização Mundial da Saúde (OMS) cerca de 90% da população mundial sofre com algum grau de estresse tornando-o uma inevitabilidade. Sabe-se que o estresse excessivo pode precipitar psicopatologias, como depressão e ansiedade, bem como alterar a funcionalidade gastrointestinal e a microbiota. Desta forma, favorecendo o desenvolvimento de distúrbios gastrointestinais funcionais (DGIFs), os quais são definidos por uma desregulação na interação cérebro-intestino. Neste contexto, modelos animais de estresse tornam-se uma ferramenta para melhor elucidar os mecanismos envolvidos nessa interação. Entretanto, grande parte dos modelos utilizados para induzir os DGIFs são crônicos ou apresentam validade limitada. Deste modo, o objetivo desse trabalho foi investigar se um modelo de estresse emocional induz DGIF, através da interação bidirecional cérebro-intestino, medeada por fenótipo do tipo depressivo/ansioso, disfunção intestinal e modulação da microbiota bacteriana intestinal em camundongos Swiss machos adultos. Este trabalho foi aprovado pelo Comitê de Ética no uso de animais da UFSM sob número #1535120320. Primeiramente, os animais foram dividos em dois grupos [Controle e Estresse Prolongado Único-Emocional (E-SPS)], camundongos do grupo E-SPS foram submetidos à exposição sequencial única a três estressores: imobilização (2h), natação forçada (15 min), seguida de recuperação (15 min), e por fim exposição ao odor do predador (3 min). Após 7 dias (período de incubação), os animais foram avaliados nos testes comportamentais preditivos de depressão e ansiedade. Os parâmetros número de peletes fecais e o teor de umidade fecal (%) foram determinados. Após 24h, amostras de fezes, sangue e tecido do cólon foram coletados para as analises. Os resultados evidenciam que os animais submetidos ao E-SPS apresentaram fenótipos do tipo depressivo e ansioso em testes comportamentais preditivos de depressão (teste de suspensão da cauda, e do nado forçado, e splash test) e ansiedade (teste do labirinto em cruz elevado), sugerindo a interação cérebro-intestino. Assim como, alterações na funcionalidade intestinal caracterizadas por aumento do trânsito intestinal, número de peletes fecais e teor de umidade fecal, além de aumento da permeabilidade intestinal relacionada a diminuição de proteínas da junção epitelial, significativamente de Claudina-1. Ainda, a exposição ao E-SPS modulou o perfil e a diversidade da microbiota intestinal dos animais quando comparados aos do grupo não estressado. Especificamente, diminuição da abundância relativa do filo Bacteroidetes, classe Bacteroidia, ordem Bacteroidales, família Muribaculaceae e Porphyromonadaceae, bem como aumento dos filos Firmicutes e Actinobacteria, ordem Coriobacteriales, e a razão de Firmicutes/Bacteroidetes e a presença do gênero Mucispirillum. Em conjunto, os resultados aqui apresentados demonstram que o modelo E-SPS induziu DGIF, através da interação cérebro-intestino, mediada por alterações comportamentais, disfunção intestinal e modulação da microbiota bacteriana intestinal em camundongos Swiss machos adultos.porUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessEstresseDistúrbio gastrointestinal funcionalCérebro-intestinoMicrobiotaStressFunctional gastrointestinal disorderBrain-gutMicrobiotaCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEstresse prolongado único-emocional induz distúrbio gastrointestinal funcional: um modelo de interação cérebro-intestinoEmotional-single prolonged stress induces functional gastrointestinal disorder: a brain-gut interaction modelinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisZeni, Gilson Rogériohttp://lattes.cnpq.br/2355575631197937Nogueira, Cristina WayneBrüning, César AugustoFachinetto, Roseleihttp://lattes.cnpq.br/2547828075068493Marques, Luiza Souza200800000002600600600600600600b21a898a-0ab0-4f33-b980-2b55ef590b946ecf1221-0da2-4d8b-a544-c537cbad93f3c2b1a64f-5f22-4779-9732-0c543f42b42d264d170b-fa65-457a-ab0a-b44bf3cfb2436a615e4f-285a-4d77-aeb6-a33cd9c07f80reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMLICENSElicense.txtlicense.txttext/plain; charset=utf-81956http://repositorio.ufsm.br/bitstream/1/26275/3/license.txt2f0571ecee68693bd5cd3f17c1e075dfMD53ORIGINALDIS_PPGBT_2022_MARQUES_LUIZA.pdfDIS_PPGBT_2022_MARQUES_LUIZA.pdfDissertação de mestradoapplication/pdf3542453http://repositorio.ufsm.br/bitstream/1/26275/1/DIS_PPGBT_2022_MARQUES_LUIZA.pdf1679d046e59212e258a11eafb34d00c7MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.ufsm.br/bitstream/1/26275/2/license_rdf4460e5956bc1d1639be9ae6146a50347MD521/262752022-09-27 14:40:04.239oai:repositorio.ufsm.br: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 Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-09-27T17:40:04Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Estresse prolongado único-emocional induz distúrbio gastrointestinal funcional: um modelo de interação cérebro-intestino |
dc.title.alternative.eng.fl_str_mv |
Emotional-single prolonged stress induces functional gastrointestinal disorder: a brain-gut interaction model |
title |
Estresse prolongado único-emocional induz distúrbio gastrointestinal funcional: um modelo de interação cérebro-intestino |
spellingShingle |
Estresse prolongado único-emocional induz distúrbio gastrointestinal funcional: um modelo de interação cérebro-intestino Marques, Luiza Souza Estresse Distúrbio gastrointestinal funcional Cérebro-intestino Microbiota Stress Functional gastrointestinal disorder Brain-gut Microbiota CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Estresse prolongado único-emocional induz distúrbio gastrointestinal funcional: um modelo de interação cérebro-intestino |
title_full |
Estresse prolongado único-emocional induz distúrbio gastrointestinal funcional: um modelo de interação cérebro-intestino |
title_fullStr |
Estresse prolongado único-emocional induz distúrbio gastrointestinal funcional: um modelo de interação cérebro-intestino |
title_full_unstemmed |
Estresse prolongado único-emocional induz distúrbio gastrointestinal funcional: um modelo de interação cérebro-intestino |
title_sort |
Estresse prolongado único-emocional induz distúrbio gastrointestinal funcional: um modelo de interação cérebro-intestino |
author |
Marques, Luiza Souza |
author_facet |
Marques, Luiza Souza |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Zeni, Gilson Rogério |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/2355575631197937 |
dc.contributor.advisor-co1.fl_str_mv |
Nogueira, Cristina Wayne |
dc.contributor.referee1.fl_str_mv |
Brüning, César Augusto |
dc.contributor.referee2.fl_str_mv |
Fachinetto, Roselei |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2547828075068493 |
dc.contributor.author.fl_str_mv |
Marques, Luiza Souza |
contributor_str_mv |
Zeni, Gilson Rogério Nogueira, Cristina Wayne Brüning, César Augusto Fachinetto, Roselei |
dc.subject.por.fl_str_mv |
Estresse Distúrbio gastrointestinal funcional Cérebro-intestino Microbiota |
topic |
Estresse Distúrbio gastrointestinal funcional Cérebro-intestino Microbiota Stress Functional gastrointestinal disorder Brain-gut Microbiota CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Stress Functional gastrointestinal disorder Brain-gut Microbiota |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Currently, about 90% of the world’s population suffers from some degree of stress, making it an inevitability (WHO). It is known that excessive stress can precipitate psychopathologies, such as depression and anxiety, and alter gastrointestinal functionality and microbiota. Consequently, favoring the development of functional gastrointestinal disorders (FGIDs), which are defined by deregulation in the brain-gut interaction. In this context, animal models of stress become a tool useful to elucidate the mechanisms involved in this interaction. However, most FGIDs models are chronic or have limited validity. Therefore, this study aimed to investigate whether a model of emotional stress induces FGID, through bidirectional braingut interaction mediated by depressive/anxious-like phenotype, intestinal dysfunction, and modulation of intestinal bacterial microbiota in adult male Swiss mice. This study was approved by the UFSM Ethics Committee on the use of animals under number # 1535120320. First, the animals were divided into two groups [Control and Emotional-Single Prolonged Stress (ESPS)], mice in the E-SPS group were subjected to a single sequential exposure to three stressors: immobilization (2h), forced swimming (15min), followed by recovery (15min), and finally exposure to predator odor (3min). After 7 days (incubation period), the animals were evaluated in behavioral tests predictive of depression and anxiety. The parameters, the number of fecal pellets and fecal moisture content (%), were determined. After 24h, samples of stool, blood, and colon tissue were collected for analysis. The results showed depressive- and anxious-like phenotypes in animals subjected to the E-SPS demonstrated in tests predictive of depression (tail suspension test, forced swimming, and splash test) and anxiety (elevated plus maze test), suggesting the brain-gut interaction. E-SPS mice had the intestinal functionality altered, increased intestinal transit, number of fecal pellets and, fecal moisture content, and increased intestinal permeability, associated with a decrease in epithelial junction proteins, significantly Claudin-1. Furthermore, exposure to E-SPS modulated the profile and diversity of the intestinal microbiota of the animals when compared to the non-stressed group. Specifically, a decrease in the relative abundance of the phylum Bacteroidetes, class Bacteroidia, order Bacteroidales, family Muribaculaceae and Prophyromonadaceae, as well as an increase in the phyla Firmicutes and Actinobacteria, order Coriobacteriales, and the Firmicutes/Bacteroidetes ratio and the presence of the genus Mucispirillum. Taken together, the results demonstrated that the E-SPS model induced FGID, through the brain-gut interaction, mediated by behavioral changes, intestinal dysfunction, and modulation of the intestinal bacterial microbiota in male Swiss mice. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-09-27T17:40:04Z |
dc.date.available.fl_str_mv |
2022-09-27T17:40:04Z |
dc.date.issued.fl_str_mv |
2022-08-30 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/26275 |
url |
http://repositorio.ufsm.br/handle/1/26275 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
200800000002 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações do UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
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