Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation

Detalhes bibliográficos
Autor(a) principal: Francesca, Pistollato
Data de Publicação: 2022
Outros Autores: Mauro, Petrillo, Clerbaux, Laure Alix, Leoni, Gabriele, Ponti, Jessica, Bogni, Alessia, Brogna, Carlo, Cristoni, Simone, Sanges, Remo, Mendoza-de Gyves, Emilio, Fabbri, Marco, Querci, Maddalena, Soares, Helena, Munoz, Amalia, Whelan, Maurice, Van de Eede, Guy
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/147355
Resumo: Funding Information: The authors would like to thank Dr. Marc Peschanski (I-Stem, Évry, France) for providing IMR90-hiPSCs, and Dr. Anna Navarro Cuenca for providing the license for the use of BioRender.com. Publisher Copyright: © 2022
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spelling Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiationPossible implications for SARS-CoV-2 impact on brain development3D neurospheresAOPbrain developmentCIAO ProjectElectrical activityRNA-SeqSpike proteinToxin-like peptidesToxicologyFunding Information: The authors would like to thank Dr. Marc Peschanski (I-Stem, Évry, France) for providing IMR90-hiPSCs, and Dr. Anna Navarro Cuenca for providing the license for the use of BioRender.com. Publisher Copyright: © 2022The possible neurodevelopmental consequences of SARS-CoV-2 infection are presently unknown. In utero exposure to SARS-CoV-2 has been hypothesized to affect the developing brain, possibly disrupting neurodevelopment of children. Spike protein interactors, such as ACE2, have been found expressed in the fetal brain, and could play a role in potential SARS-CoV-2 fetal brain pathogenesis. Apart from the possible direct involvement of SARS-CoV-2 or its specific viral components in the occurrence of neurological and neurodevelopmental manifestations, we recently reported the presence of toxin-like peptides in plasma, urine and fecal samples specifically from COVID-19 patients. In this study, we investigated the possible neurotoxic effects elicited upon 72-hour exposure to human relevant levels of recombinant spike protein, toxin-like peptides found in COVID-19 patients, as well as a combination of both in 3D human iPSC-derived neural stem cells differentiated for either 2 weeks (short-term) or 8 weeks (long-term, 2 weeks in suspension + 6 weeks on MEA) towards neurons/glia. Whole transcriptome and qPCR analysis revealed that spike protein and toxin-like peptides at non-cytotoxic concentrations differentially perturb the expression of SPHK1, ELN, GASK1B, HEY1, UTS2, ACE2 and some neuronal-, glia- and NSC-related genes critical during brain development. Additionally, exposure to spike protein caused a decrease of spontaneous electrical activity after two days in long-term differentiated cultures. The perturbations of these neurodevelopmental endpoints are discussed in the context of recent knowledge about the key events described in Adverse Outcome Pathways relevant to COVID-19, gathered in the context of the CIAO project (https://www.ciao-covid.net/).NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNFrancesca, PistollatoMauro, PetrilloClerbaux, Laure AlixLeoni, GabrielePonti, JessicaBogni, AlessiaBrogna, CarloCristoni, SimoneSanges, RemoMendoza-de Gyves, EmilioFabbri, MarcoQuerci, MaddalenaSoares, HelenaMunoz, AmaliaWhelan, MauriceVan de Eede, Guy2023-01-11T22:16:31Z2022-082022-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article15application/pdfhttp://hdl.handle.net/10362/147355eng0890-6238PURE: 44791991https://doi.org/10.1016/j.reprotox.2022.04.011info: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:RCAAP2024-03-11T05:28:26Zoai:run.unl.pt:10362/147355Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:52:52.972942Repositório 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 Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation
Possible implications for SARS-CoV-2 impact on brain development
title Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation
spellingShingle Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation
Francesca, Pistollato
3D neurospheres
AOP
brain development
CIAO Project
Electrical activity
RNA-Seq
Spike protein
Toxin-like peptides
Toxicology
title_short Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation
title_full Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation
title_fullStr Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation
title_full_unstemmed Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation
title_sort Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation
author Francesca, Pistollato
author_facet Francesca, Pistollato
Mauro, Petrillo
Clerbaux, Laure Alix
Leoni, Gabriele
Ponti, Jessica
Bogni, Alessia
Brogna, Carlo
Cristoni, Simone
Sanges, Remo
Mendoza-de Gyves, Emilio
Fabbri, Marco
Querci, Maddalena
Soares, Helena
Munoz, Amalia
Whelan, Maurice
Van de Eede, Guy
author_role author
author2 Mauro, Petrillo
Clerbaux, Laure Alix
Leoni, Gabriele
Ponti, Jessica
Bogni, Alessia
Brogna, Carlo
Cristoni, Simone
Sanges, Remo
Mendoza-de Gyves, Emilio
Fabbri, Marco
Querci, Maddalena
Soares, Helena
Munoz, Amalia
Whelan, Maurice
Van de Eede, Guy
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Francesca, Pistollato
Mauro, Petrillo
Clerbaux, Laure Alix
Leoni, Gabriele
Ponti, Jessica
Bogni, Alessia
Brogna, Carlo
Cristoni, Simone
Sanges, Remo
Mendoza-de Gyves, Emilio
Fabbri, Marco
Querci, Maddalena
Soares, Helena
Munoz, Amalia
Whelan, Maurice
Van de Eede, Guy
dc.subject.por.fl_str_mv 3D neurospheres
AOP
brain development
CIAO Project
Electrical activity
RNA-Seq
Spike protein
Toxin-like peptides
Toxicology
topic 3D neurospheres
AOP
brain development
CIAO Project
Electrical activity
RNA-Seq
Spike protein
Toxin-like peptides
Toxicology
description Funding Information: The authors would like to thank Dr. Marc Peschanski (I-Stem, Évry, France) for providing IMR90-hiPSCs, and Dr. Anna Navarro Cuenca for providing the license for the use of BioRender.com. Publisher Copyright: © 2022
publishDate 2022
dc.date.none.fl_str_mv 2022-08
2022-08-01T00:00:00Z
2023-01-11T22:16:31Z
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/10362/147355
url http://hdl.handle.net/10362/147355
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0890-6238
PURE: 44791991
https://doi.org/10.1016/j.reprotox.2022.04.011
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 15
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
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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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