TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice

Detalhes bibliográficos
Autor(a) principal: Obadia, Nathalie
Data de Publicação: 2022
Outros Autores: Andrade, Giulia, Leardini-Tristão, Marina, Albuquerque, Letícia, Garcia, Celina, Lima, Flavia, Daleprane, Júlio, Faria Neto, Hugo C. Castro, Tibiriçá, Eduardo, Estato, Vanessa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/53249
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
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spelling Obadia, NathalieAndrade, GiuliaLeardini-Tristão, MarinaAlbuquerque, LetíciaGarcia, CelinaLima, FlaviaDaleprane, JúlioFaria Neto, Hugo C. CastroTibiriçá, EduardoEstato, Vanessa2022-06-14T13:02:44Z2022-06-14T13:02:44Z2022OBADIA, Nathalie et al. TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice. Journal of Neuroinflammation, v. 19, 104, p. 1 - 18, 2022.1742-2084https://www.arca.fiocruz.br/handle/icict/5324910.1186/s12974-022-02465-3engBMCMicrocirculação cerebralConsumo de dieta rica em gorduraTLR4NeuroinflamaçãoCélulas da gliaBrain microcirculationHigh-fat diet consumptionTLR4NeuroinflammationGlial cellsTLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Glial Biologia Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Glial Biologia Celular. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Laboratório Interdisciplinar de Avaliação Nutricional. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Cardiologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Background: Metabolic syndrome (MS) is defined as a low-grade proinflammatory state in which abnormal metabolic and cardiovascular factors increase the risk of developing cardiovascular disease and neuroinflammation. Events, such as the accumulation of visceral adipose tissue, increased plasma concentrations of free fatty acids, tissue hypoxia, and sympathetic hyperactivity in MS may contribute to the direct or indirect activation of Toll-like receptors (TLRs), specifically TLR4, which is thought to be a major component of this syndrome. Activation of the innate immune response via TLR4 may contribute to this state of chronic inflammation and may be related to the neuroinflammation and neurodegeneration observed in MS. In this study, we investigated the role of TLR4 in the brain microcirculation and in the cognitive performance of high-fat diet (HFD)-induced MS mice. Methods: Wild-type (C3H/He) and TLR4 mutant (C3H/HeJ) mice were maintained under a normal diet (ND) or a HFD for 24 weeks. Intravital video-microscopy was used to investigate the functional capillary density, endothelial function, and endothelial–leukocyte interactions in the brain microcirculation. Plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), adipokines and metabolic hormones were measured with a multiplex immunoassay. Brain postsynaptic density protein-95 and synaptophysin were evaluated by western blotting; astrocytic coverage of the vessels, microglial activation and structural capillary density were evaluated by immunohistochemistry. Results: The HFD-induced MS model leads to metabolic, hemodynamic, and microcirculatory alterations, as evidenced by capillary rarefaction, increased rolling and leukocyte adhesion in postcapillary venules, endothelial dysfunction, and less coverage of astrocytes in the vessels, which are directly related to cognitive decline and neuroinflammation. The same model of MS reproduced in mice deficient for TLR4 because of a genetic mutation does not generate such changes. Furthermore, the comparison of wild-type mice fed a HFD and a normolipid diet revealed differences in inflammation in the cerebral microcirculation, possibly related to lower TLR4 activation. Conclusions: Our results demonstrate that TLR4 is involved in the microvascular dysfunction and neuroinflammation associated with HFD-induced MS and possibly has a causal role in the development of cognitive decline.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/53249/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALNathalieObadia_VanessaEstato_HugoCastro_etal_IOC_2022.pdfNathalieObadia_VanessaEstato_HugoCastro_etal_IOC_2022.pdfapplication/pdf3443275https://www.arca.fiocruz.br/bitstream/icict/53249/2/NathalieObadia_VanessaEstato_HugoCastro_etal_IOC_2022.pdf53f31f1dd0d6825a50e6983caafbe5b7MD52icict/532492022-06-14 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dc.title.pt_BR.fl_str_mv TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice
title TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice
spellingShingle TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice
Obadia, Nathalie
Microcirculação cerebral
Consumo de dieta rica em gordura
TLR4
Neuroinflamação
Células da glia
Brain microcirculation
High-fat diet consumption
TLR4
Neuroinflammation
Glial cells
title_short TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice
title_full TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice
title_fullStr TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice
title_full_unstemmed TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice
title_sort TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice
author Obadia, Nathalie
author_facet Obadia, Nathalie
Andrade, Giulia
Leardini-Tristão, Marina
Albuquerque, Letícia
Garcia, Celina
Lima, Flavia
Daleprane, Júlio
Faria Neto, Hugo C. Castro
Tibiriçá, Eduardo
Estato, Vanessa
author_role author
author2 Andrade, Giulia
Leardini-Tristão, Marina
Albuquerque, Letícia
Garcia, Celina
Lima, Flavia
Daleprane, Júlio
Faria Neto, Hugo C. Castro
Tibiriçá, Eduardo
Estato, Vanessa
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Obadia, Nathalie
Andrade, Giulia
Leardini-Tristão, Marina
Albuquerque, Letícia
Garcia, Celina
Lima, Flavia
Daleprane, Júlio
Faria Neto, Hugo C. Castro
Tibiriçá, Eduardo
Estato, Vanessa
dc.subject.other.pt_BR.fl_str_mv Microcirculação cerebral
Consumo de dieta rica em gordura
TLR4
Neuroinflamação
Células da glia
topic Microcirculação cerebral
Consumo de dieta rica em gordura
TLR4
Neuroinflamação
Células da glia
Brain microcirculation
High-fat diet consumption
TLR4
Neuroinflammation
Glial cells
dc.subject.en.pt_BR.fl_str_mv Brain microcirculation
High-fat diet consumption
TLR4
Neuroinflammation
Glial cells
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-06-14T13:02:44Z
dc.date.available.fl_str_mv 2022-06-14T13:02:44Z
dc.date.issued.fl_str_mv 2022
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv OBADIA, Nathalie et al. TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice. Journal of Neuroinflammation, v. 19, 104, p. 1 - 18, 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/53249
dc.identifier.issn.pt_BR.fl_str_mv 1742-2084
dc.identifier.doi.none.fl_str_mv 10.1186/s12974-022-02465-3
identifier_str_mv OBADIA, Nathalie et al. TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice. Journal of Neuroinflammation, v. 19, 104, p. 1 - 18, 2022.
1742-2084
10.1186/s12974-022-02465-3
url https://www.arca.fiocruz.br/handle/icict/53249
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.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/53249/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/53249/2/NathalieObadia_VanessaEstato_HugoCastro_etal_IOC_2022.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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