Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation

Bibliographic Details
Main Author: Machado-Pereira, Marta
Publication Date: 2022
Other Authors: Saraiva, Cláudia, Bernardino, Liliana, Cristóvão, Ana C., Ferreira, Raquel
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/131573
Summary: Funding PPBI—Portuguese Platform of BioImaging, POCI-01-0145-FEDER-022122; FCT—Fundação para a Ciência e Tecnologia, UID/Multi/00709/2013, SFRH/ BD/137440/2018 (MMP), IF/00178/2015/CP1300/CT0001 (RF); FCT—L’Oréal— UNESCO Portugal for Women in Science (RF).
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network_acronym_str RCAP
network_name_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
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spelling Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammationArgonaute-2Brain endothelial cellsGliaLipopolysaccharideNeuroprotectionSecretomeNeuroscience(all)ImmunologyNeurologyCellular and Molecular NeuroscienceFunding PPBI—Portuguese Platform of BioImaging, POCI-01-0145-FEDER-022122; FCT—Fundação para a Ciência e Tecnologia, UID/Multi/00709/2013, SFRH/ BD/137440/2018 (MMP), IF/00178/2015/CP1300/CT0001 (RF); FCT—L’Oréal— UNESCO Portugal for Women in Science (RF).Background: The brain vasculature plays a pivotal role in the inflammatory process by modulating the interaction between blood cells and the neurovascular unit. Argonaute-2 (Ago2) has been suggested as essential for endothelial survival but its role in the brain vasculature or in the endothelial–glial crosstalk has not been addressed. Thus, our aim was to clarify the significance of Ago2 in the inflammatory responses elicited by these cell types. Methods: Mouse primary cultures of brain endothelial cells, astrocytes and microglia were used to evaluate cellular responses to the modulation of Ago2. Exposure of microglia to endothelial cell-conditioned media was used to assess the potential for in vivo studies. Adult mice were injected intraperitoneally with lipopolysaccharide (LPS) (2 mg/kg) followed by three daily intraperitoneal injections of Ago2 (0.4 nM) to assess markers of endothelial disruption, glial reactivity and neuronal function. Results: Herein, we demonstrated that LPS activation disturbed the integrity of adherens junctions and downregulated Ago2 in primary brain endothelial cells. Exogenous treatment recovered intracellular Ago2 above control levels and recuperated vascular endothelial-cadherin expression, while downregulating LPS-induced nitric oxide release. Primary astrocytes did not show a significant change in Ago2 levels or response to the modulation of the Ago2 system, although endogenous Ago2 was shown to be critical in the maintenance of tumor necrosis factor-α basal levels. LPS-activated primary microglia overexpressed Ago2, and Ago2 silencing contained the inflammatory response to some extent, preventing interleukin-6 and nitric oxide release. Moreover, the secretome of Ago2-modulated brain endothelial cells had a protective effect over microglia. The intraperitoneal injection of LPS impaired blood–brain barrier and neuronal function, while triggering inflammation, and the subsequent systemic administration of Ago2 reduced or normalized endothelial, glial and neuronal markers of LPS damage. This outcome likely resulted from the direct action of Ago2 over the brain endothelium, which reestablished glial and neuronal function. Conclusions: Ago2 could be regarded as a putative therapeutic agent, or target, in the recuperation of the neurovascular unit in inflammatory conditions.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNMachado-Pereira, MartaSaraiva, CláudiaBernardino, LilianaCristóvão, Ana C.Ferreira, Raquel2022-01-26T03:31:41Z2022-01-062022-01-06T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/131573engPURE: 36216027https://doi.org/10.1186/s12974-021-02324-7info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-27T01:39:20Zoai:run.unl.pt:10362/131573Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:29:36.951588Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation
title Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation
spellingShingle Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation
Machado-Pereira, Marta
Argonaute-2
Brain endothelial cells
Glia
Lipopolysaccharide
Neuroprotection
Secretome
Neuroscience(all)
Immunology
Neurology
Cellular and Molecular Neuroscience
title_short Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation
title_full Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation
title_fullStr Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation
title_full_unstemmed Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation
title_sort Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation
author Machado-Pereira, Marta
author_facet Machado-Pereira, Marta
Saraiva, Cláudia
Bernardino, Liliana
Cristóvão, Ana C.
Ferreira, Raquel
author_role author
author2 Saraiva, Cláudia
Bernardino, Liliana
Cristóvão, Ana C.
Ferreira, Raquel
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Machado-Pereira, Marta
Saraiva, Cláudia
Bernardino, Liliana
Cristóvão, Ana C.
Ferreira, Raquel
dc.subject.por.fl_str_mv Argonaute-2
Brain endothelial cells
Glia
Lipopolysaccharide
Neuroprotection
Secretome
Neuroscience(all)
Immunology
Neurology
Cellular and Molecular Neuroscience
topic Argonaute-2
Brain endothelial cells
Glia
Lipopolysaccharide
Neuroprotection
Secretome
Neuroscience(all)
Immunology
Neurology
Cellular and Molecular Neuroscience
description Funding PPBI—Portuguese Platform of BioImaging, POCI-01-0145-FEDER-022122; FCT—Fundação para a Ciência e Tecnologia, UID/Multi/00709/2013, SFRH/ BD/137440/2018 (MMP), IF/00178/2015/CP1300/CT0001 (RF); FCT—L’Oréal— UNESCO Portugal for Women in Science (RF).
publishDate 2022
dc.date.none.fl_str_mv 2022-01-26T03:31:41Z
2022-01-06
2022-01-06T00:00:00Z
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.uri.fl_str_mv http://hdl.handle.net/10362/131573
url http://hdl.handle.net/10362/131573
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PURE: 36216027
https://doi.org/10.1186/s12974-021-02324-7
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:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
_version_ 1833596734005051392

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