SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome inmice
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2023 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/57715 |
Resumo: | 2023 |
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Dantas, Fabricia L. FontesFernandes, Gabriel G.Gutman, Elisa G.Lima, Emanuelle V. DeAntonio, Leticia S.Hammerle, Mariana B.Araujo, Hannah P. MotaColodeti, LilianAraujo, Suzana M. B.Froz, Gabrielle M.Silva, Talita N. daDuarte, Larissa A.Salvio, Andreza L.Pires, Karina L.Leon, Luciane A. A.Vasconcelos, Claudia Cristina F.Romão, LucianaSavio, Luiz Eduardo B.Silva, Jerson L.Costa, Robson daClarke, Julia R.Da Poian, Andrea T.Leon, Soniza V. AlvesPassos, Giselle F.Figueiredo, Claudia P.2023-04-07T16:55:02Z2023-04-07T16:55:02Z2023DANTAS, Fabricia L. Fontes et al. SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice. Cell Rep, v. 42, n. 3, 112189, p. 1 - 23, Mar. 2023.2639-1856https://www.arca.fiocruz.br/handle/icict/5771510.1016/j.celrep.2023.112189engNational Library of MedicineDisfunção cognitivaProteína spike SARS-CoV-2NeuroinflamaçãoPerda de sinapsePoda sinápticaTLR4Variante genéticaCOVID longaSíndrome pós-COVIDMicroglioseCognitive dysfunctionSARS-CoV-2 spike proteinNeuroinflammationMicrogliosisSynapse lossSynaptic pruningTLR4Genetic variantLong COVIDPost-COVID syndromeSARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome inmiceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2023Universidade Federal do Rio de Janeiro. Escola de Farmácia. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Instituto de Biologia. Departamento de Farmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Escola de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Programa de Pós-Graduação emNeurologia. Laboratório de Neurociência Translacional (LabNet). Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Programa de Pós Graduação em Medicina Clínica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Escola de Farmácia. Rio de Janeiro, RJ, BrasilUniversidade Federal do Rio de Janeiro. Escola de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Programa de Pós Graduação em Medicina Clínica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Escola de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Escola de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Escola de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Escola de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Escola de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Programa de Pós-Graduação emNeurologia. Laboratório de Neurociência Translacional (LabNet). Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Programa de Pós Graduação em Medicina Clínica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Programa de Pós-Graduação emNeurologia. Laboratório de Neurociência Translacional (LabNet). Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. (UNIRIO). Departamento de Neurologia. Rio de janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Desenvolvimento Tecnológico em Virologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. (UNIRIO). Departamento de Neurologia. Rio de janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Escola de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Programa de Pós-Graduação em Neurologia. Laboratório de Neurociência Translacional (LabNet). Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Hospital Clementino Frga Filho. Divisão de Neurologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Escola de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Escola de Farmácia. Rio de Janeiro, RJ, Brasil,Cognitive dysfunction is often reported in patients with post-coronavirus disease 2019 (COVID-19) syndrome, but its underlying mechanisms are not completely understood. Evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein or its fragments are released from cells during infection, reaching different tissues, including the CNS, irrespective of the presence of the viral RNA. Here, we demonstrate that brain infusion of Spike protein in mice has a late impact on cognitive function, recapitulating post-COVID-19 syndrome. We also show that neuroinflammation and hippocampal microgliosis mediate Spike-induced memory dysfunction via complement-dependent engulfment of synapses. Genetic or pharmacological blockage of Toll-like receptor 4 (TLR4) signaling protects animals against synapse elimination and memory dysfunction induced by Spike brain infusion. Accordingly, in a cohort of 86 patients who recovered from mild COVID-19, the genotype GG TLR4-2604G>A (rs10759931) is associated with poor cognitive outcome. These results identify TLR4 as a key target to investigate the long-term cognitive dysfunction after COVID-19 infection in humans and rodents.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/57715/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALLucianeLeon_FabriciaDantas_etal_IOC_2023.pdfLucianeLeon_FabriciaDantas_etal_IOC_2023.pdfapplication/pdf4846887https://www.arca.fiocruz.br/bitstream/icict/57715/2/LucianeLeon_FabriciaDantas_etal_IOC_2023.pdf098219bb926aafa0527a079278e3cc8dMD52icict/577152023-09-14 15:46:54.804oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-14T18:46:54Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.en_US.fl_str_mv |
SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome inmice |
| title |
SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome inmice |
| spellingShingle |
SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome inmice Dantas, Fabricia L. Fontes Disfunção cognitiva Proteína spike SARS-CoV-2 Neuroinflamação Perda de sinapse Poda sináptica TLR4 Variante genética COVID longa Síndrome pós-COVID Microgliose Cognitive dysfunction SARS-CoV-2 spike protein Neuroinflammation Microgliosis Synapse loss Synaptic pruning TLR4 Genetic variant Long COVID Post-COVID syndrome |
| title_short |
SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome inmice |
| title_full |
SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome inmice |
| title_fullStr |
SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome inmice |
| title_full_unstemmed |
SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome inmice |
| title_sort |
SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome inmice |
| author |
Dantas, Fabricia L. Fontes |
| author_facet |
Dantas, Fabricia L. Fontes Fernandes, Gabriel G. Gutman, Elisa G. Lima, Emanuelle V. De Antonio, Leticia S. Hammerle, Mariana B. Araujo, Hannah P. Mota Colodeti, Lilian Araujo, Suzana M. B. Froz, Gabrielle M. Silva, Talita N. da Duarte, Larissa A. Salvio, Andreza L. Pires, Karina L. Leon, Luciane A. A. Vasconcelos, Claudia Cristina F. Romão, Luciana Savio, Luiz Eduardo B. Silva, Jerson L. Costa, Robson da Clarke, Julia R. Da Poian, Andrea T. Leon, Soniza V. Alves Passos, Giselle F. Figueiredo, Claudia P. |
| author_role |
author |
| author2 |
Fernandes, Gabriel G. Gutman, Elisa G. Lima, Emanuelle V. De Antonio, Leticia S. Hammerle, Mariana B. Araujo, Hannah P. Mota Colodeti, Lilian Araujo, Suzana M. B. Froz, Gabrielle M. Silva, Talita N. da Duarte, Larissa A. Salvio, Andreza L. Pires, Karina L. Leon, Luciane A. A. Vasconcelos, Claudia Cristina F. Romão, Luciana Savio, Luiz Eduardo B. Silva, Jerson L. Costa, Robson da Clarke, Julia R. Da Poian, Andrea T. Leon, Soniza V. Alves Passos, Giselle F. Figueiredo, Claudia P. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Dantas, Fabricia L. Fontes Fernandes, Gabriel G. Gutman, Elisa G. Lima, Emanuelle V. De Antonio, Leticia S. Hammerle, Mariana B. Araujo, Hannah P. Mota Colodeti, Lilian Araujo, Suzana M. B. Froz, Gabrielle M. Silva, Talita N. da Duarte, Larissa A. Salvio, Andreza L. Pires, Karina L. Leon, Luciane A. A. Vasconcelos, Claudia Cristina F. Romão, Luciana Savio, Luiz Eduardo B. Silva, Jerson L. Costa, Robson da Clarke, Julia R. Da Poian, Andrea T. Leon, Soniza V. Alves Passos, Giselle F. Figueiredo, Claudia P. |
| dc.subject.other.en_US.fl_str_mv |
Disfunção cognitiva Proteína spike SARS-CoV-2 Neuroinflamação Perda de sinapse Poda sináptica TLR4 Variante genética COVID longa Síndrome pós-COVID Microgliose |
| topic |
Disfunção cognitiva Proteína spike SARS-CoV-2 Neuroinflamação Perda de sinapse Poda sináptica TLR4 Variante genética COVID longa Síndrome pós-COVID Microgliose Cognitive dysfunction SARS-CoV-2 spike protein Neuroinflammation Microgliosis Synapse loss Synaptic pruning TLR4 Genetic variant Long COVID Post-COVID syndrome |
| dc.subject.en.en_US.fl_str_mv |
Cognitive dysfunction SARS-CoV-2 spike protein Neuroinflammation Microgliosis Synapse loss Synaptic pruning TLR4 Genetic variant Long COVID Post-COVID syndrome |
| description |
2023 |
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2023 |
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2023-04-07T16:55:02Z |
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2023-04-07T16:55:02Z |
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2023 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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DANTAS, Fabricia L. Fontes et al. SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice. Cell Rep, v. 42, n. 3, 112189, p. 1 - 23, Mar. 2023. |
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https://www.arca.fiocruz.br/handle/icict/57715 |
| dc.identifier.issn.en_US.fl_str_mv |
2639-1856 |
| dc.identifier.doi.none.fl_str_mv |
10.1016/j.celrep.2023.112189 |
| identifier_str_mv |
DANTAS, Fabricia L. Fontes et al. SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice. Cell Rep, v. 42, n. 3, 112189, p. 1 - 23, Mar. 2023. 2639-1856 10.1016/j.celrep.2023.112189 |
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https://www.arca.fiocruz.br/handle/icict/57715 |
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eng |
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eng |
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National Library of Medicine |
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National Library of Medicine |
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