Human phenolic metabolites as modulators of neuroinflammation

Detalhes bibliográficos
Autor(a) principal: Bento, Maria Inês Varela Costa de Vasconcelos
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/37233
Resumo: Tese de mestrado, Biologia Molecular e Genética, Universidade de Lisboa, Faculdade de Ciências, 2018
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spelling Human phenolic metabolites as modulators of neuroinflammationMetabolitos fenólicosNeuroinflamaçãoMicrogliaTNFαIFNγTeses de mestrado - 2018Departamento de Biologia VegetalTese de mestrado, Biologia Molecular e Genética, Universidade de Lisboa, Faculdade de Ciências, 2018Neurodegenerative diseases are characterised by progressive degeneration and loss of neurons. With the aging of the world population, their incidence is predicted to increase. As these diseases are incurable and the only existing therapies merely attenuate the symptoms, a great interest in preventing them arises. Neuroinflammation is hallmark common to many neurodegenerative diseases. It is mediated by microglia, innate immune cells resident in the central nervous system. Their main function in the healthy brain is surveillance, and they also participate in neurogenesis during development. When damage occurs, these cells become transiently activated and gain a pro-inflammatory phenotype, which is beneficial and allows them to protect the brain. However, in neurodegenerative diseases this activation becomes chronic, and microglia becomes deleterious and induces neuron loss. Phenolic compounds are phytochemicals easily obtained through a healthy diet that have been demonstrated to have anti-inflammatory properties. However, when obtained through diet, they are more likely to reach the brain as modified metabolites than as parent compounds. Importantly, to act over microglia, they must cross the blood-brain barrier. Following an intervention study where colonic phenolic metabolites were identified in circulation after consumption of a berry purée, the compounds were tested for the ability to cross the blood-brain barrier. Not only they were found to be transported across it, the same study discovered that pyrogallol-sulfate, one of the metabolites that reached the highest concentrations in circulation, could attenuate neuroinflammation in microglia. Most neuroinflammation studies use lipopolysaccharide (LPS) as a stimulus. However, its presence in the brain in vivo is unlikely. This work created a new inflammation model in murine microglia using tumour necrosis factor (TNF)α and interferon (IFN)γ, two cytokines more likely to be found in the brain and known to be increased in neurodegenerative diseases. Different concentrations were tested, and compared with the commonly used LPS insult. Several pro- and anti-inflammatory factors were evaluated to characterise cell response. After establishing the model, this work used it to assess the ability of phenolic compounds to attenuate neuroinflammation. The compounds used were catechol-sulfate and pyrogallol-sulfate, already tested in a model using LPS, and phloroglucinol-sulfate, resorcinol-sulfate and pyrogallol-glucoronide, which are chemically similar to pyrogallol. They showed different effects over different markers suggesting a pleiotropic action. Pyrogallol sulfate also showed potential to attenuate inflammation in this model.Santos, Cláudia Nunes dos, 1970-Figueiredo, Ana Cristina da Silva, 1959-Repositório da Universidade de LisboaBento, Maria Inês Varela Costa de Vasconcelos2021-12-18T01:30:15Z201820182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10451/37233TID:202192210enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:34:20Zoai:repositorio.ul.pt:10451/37233Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:51:20.618262Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Human phenolic metabolites as modulators of neuroinflammation
title Human phenolic metabolites as modulators of neuroinflammation
spellingShingle Human phenolic metabolites as modulators of neuroinflammation
Bento, Maria Inês Varela Costa de Vasconcelos
Metabolitos fenólicos
Neuroinflamação
Microglia
TNFα
IFNγ
Teses de mestrado - 2018
Departamento de Biologia Vegetal
title_short Human phenolic metabolites as modulators of neuroinflammation
title_full Human phenolic metabolites as modulators of neuroinflammation
title_fullStr Human phenolic metabolites as modulators of neuroinflammation
title_full_unstemmed Human phenolic metabolites as modulators of neuroinflammation
title_sort Human phenolic metabolites as modulators of neuroinflammation
author Bento, Maria Inês Varela Costa de Vasconcelos
author_facet Bento, Maria Inês Varela Costa de Vasconcelos
author_role author
dc.contributor.none.fl_str_mv Santos, Cláudia Nunes dos, 1970-
Figueiredo, Ana Cristina da Silva, 1959-
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Bento, Maria Inês Varela Costa de Vasconcelos
dc.subject.por.fl_str_mv Metabolitos fenólicos
Neuroinflamação
Microglia
TNFα
IFNγ
Teses de mestrado - 2018
Departamento de Biologia Vegetal
topic Metabolitos fenólicos
Neuroinflamação
Microglia
TNFα
IFNγ
Teses de mestrado - 2018
Departamento de Biologia Vegetal
description Tese de mestrado, Biologia Molecular e Genética, Universidade de Lisboa, Faculdade de Ciências, 2018
publishDate 2018
dc.date.none.fl_str_mv 2018
2018
2018-01-01T00:00:00Z
2021-12-18T01:30:15Z
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 http://hdl.handle.net/10451/37233
TID:202192210
url http://hdl.handle.net/10451/37233
identifier_str_mv TID:202192210
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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