Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life
Autor(a) principal: | |
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Data de Publicação: | 2021 |
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/46312 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de janeiro, RJ, Brasil. |
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Granja, Marcelo GomesAlves, Letícia PiresTristão, Marina LeardiniSaul, Michelle EdelmanBortoni, Letícia CoelhoMoraes, Flávia Maciel deFerreira, Érica CamilaPortugal, Bianca Tavares de MoraesSilva, Victória Zerboni daSantos, Adrielle Ferreira Ribeiro dosSilva, Adriana RibeiroAlbuquerque, Cassiano Felippe Gonçalves deBambini Junior, VictorioWeyrich, Andrew S.Rondina, Matthew T. RondinaZimmerman, Guy A.Faria Neto, Hugo Caire de Castro2021-03-09T14:09:40Z2021-03-09T14:09:40Z2021GRANJA, Marcelo Gomes et al. Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life. Journal of Neuroinflammation, v. 18, n. 60, 18p, 2021.1178-7031https://www.arca.fiocruz.br/handle/icict/4631210.1186/s12974-021-02106-1engDove PressSepse gestacionalSináfitiaDepressãoMemóriaDanos no motorGestational sepsisSynaptophysinDepressionMemoryMotor damageInflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of lifeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Estácio de Sá. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Estácio de Sá. Faculdade de Medicina. 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 Fluminense. Programa de Pós-graduação em Neurociências. Niterói, 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 Estado do Rio de Janeiro. Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de janeiro, RJ, Brasil.School of Pharmacy and Biomedical Sciences, University of Central Lancashire, PR1 2HE. Lancashire, Preston, England, UKSchool of Pharmacy and Biomedical Sciences, University of Central Lancashire, PR1 2HE. Lancashire, Preston, England, UKDepartment of Internal Medicine and Molecular Medicine Program, University of Utah. Salt Lake City, UT, USA / Department of Internal Medicine and Pathology, University of Utah. Salt Lake City, UT, USA / 8Department of Internal Medicine and GRECC, George E. Wahlen VAMC. Salt Lake City, UT, USA.Department of Internal Medicine and Molecular Medicine Program, University of Utah. Salt Lake City, UT, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Background: The term sepsis is used to designate a systemic condition of infection and inflammation associated with hemodynamic changes that result in organic dysfunction. Gestational sepsis can impair the development of the central nervous system and may promote permanent behavior alterations in the offspring. The aim of our work was to evaluate the effects of maternal sepsis on inflammatory cytokine levels and synaptic proteins in the hippocampus, neocortex, frontal cortex, and cerebellum of neonatal, young, and adult mice. Additionally, we analyzed the motor development, behavioral features, and cognitive impairments in neonatal, young and adult offspring. Methods: Pregnant mice at the 14th embryonic day (E14) were intratracheally instilled with saline 0.9% solution (control group) or Klebsiella spp. (3 × 108 CFU) (sepsis group) and started on meropenem after 5 h. The offspring was sacrificed at postnatal day (P) 2, P8, P30, and P60 and samples of liver, lung, and brain were collected for TNF-α, IL-1β, and IL-6 measurements by ELISA. Synaptophysin, PSD95, and β-tubulin levels were analyzed by Western blot. Motor tests were performed at all analyzed ages and behavioral assessments were performed in offspring at P30 and P60.Results: Gestational sepsis induces a systemic pro-inflammatory response in neonates at P2 and P8 characterized by an increase in cytokine levels. Maternal sepsis induced systemic downregulation of pro-inflammatory cytokines, while in the hippocampus, neocortex, frontal cortex, and cerebellum an inflammatory response was detected. These changes in the brain immunity were accompanied by a reduction of synaptophysin and PSD95 levels in the hippocampus, neocortex, frontal cortex, and cerebellum, in all ages. Behavioral tests demonstrated motor impairment in neonates, and depressive-like behavior, fear-conditioned memory, and learning impairments in animals at P30 and P60, while spatial memory abilities were affected only at P60, indicating that gestational sepsis not only induces an inflammatory response in neonatal mouse brains, but also affects neurodevelopment, and leads to a plethora of behavioral alterations and cognitive impairments in the offspring. Conclusion: These data suggest that maternal sepsis may be causatively related to the development of depression, learning, and memory impairments in the litter.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/46312/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALMarceloGranja_LeticiaAlves_etal_IOC_2021.pdfMarceloGranja_LeticiaAlves_etal_IOC_2021.pdfapplication/pdf2654554https://www.arca.fiocruz.br/bitstream/icict/46312/2/MarceloGranja_LeticiaAlves_etal_IOC_2021.pdf408bba646f4fa7237d3b01375a164900MD52TEXTMarceloGranja_LeticiaAlves_etal_IOC_2021.pdf.txtMarceloGranja_LeticiaAlves_etal_IOC_2021.pdf.txtExtracted texttext/plain83704https://www.arca.fiocruz.br/bitstream/icict/46312/3/MarceloGranja_LeticiaAlves_etal_IOC_2021.pdf.txtcfedc4163e20ed079ccd5033315a2e90MD53icict/463122021-03-10 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dc.title.pt_BR.fl_str_mv |
Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life |
title |
Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life |
spellingShingle |
Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life Granja, Marcelo Gomes Sepse gestacional Sináfitia Depressão Memória Danos no motor Gestational sepsis Synaptophysin Depression Memory Motor damage |
title_short |
Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life |
title_full |
Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life |
title_fullStr |
Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life |
title_full_unstemmed |
Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life |
title_sort |
Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life |
author |
Granja, Marcelo Gomes |
author_facet |
Granja, Marcelo Gomes Alves, Letícia Pires Tristão, Marina Leardini Saul, Michelle Edelman Bortoni, Letícia Coelho Moraes, Flávia Maciel de Ferreira, Érica Camila Portugal, Bianca Tavares de Moraes Silva, Victória Zerboni da Santos, Adrielle Ferreira Ribeiro dos Silva, Adriana Ribeiro Albuquerque, Cassiano Felippe Gonçalves de Bambini Junior, Victorio Weyrich, Andrew S. Rondina, Matthew T. Rondina Zimmerman, Guy A. Faria Neto, Hugo Caire de Castro |
author_role |
author |
author2 |
Alves, Letícia Pires Tristão, Marina Leardini Saul, Michelle Edelman Bortoni, Letícia Coelho Moraes, Flávia Maciel de Ferreira, Érica Camila Portugal, Bianca Tavares de Moraes Silva, Victória Zerboni da Santos, Adrielle Ferreira Ribeiro dos Silva, Adriana Ribeiro Albuquerque, Cassiano Felippe Gonçalves de Bambini Junior, Victorio Weyrich, Andrew S. Rondina, Matthew T. Rondina Zimmerman, Guy A. Faria Neto, Hugo Caire de Castro |
author2_role |
author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Granja, Marcelo Gomes Alves, Letícia Pires Tristão, Marina Leardini Saul, Michelle Edelman Bortoni, Letícia Coelho Moraes, Flávia Maciel de Ferreira, Érica Camila Portugal, Bianca Tavares de Moraes Silva, Victória Zerboni da Santos, Adrielle Ferreira Ribeiro dos Silva, Adriana Ribeiro Albuquerque, Cassiano Felippe Gonçalves de Bambini Junior, Victorio Weyrich, Andrew S. Rondina, Matthew T. Rondina Zimmerman, Guy A. Faria Neto, Hugo Caire de Castro |
dc.subject.other.pt_BR.fl_str_mv |
Sepse gestacional Sináfitia Depressão Memória Danos no motor |
topic |
Sepse gestacional Sináfitia Depressão Memória Danos no motor Gestational sepsis Synaptophysin Depression Memory Motor damage |
dc.subject.en.pt_BR.fl_str_mv |
Gestational sepsis Synaptophysin Depression Memory Motor damage |
description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de janeiro, RJ, Brasil. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-03-09T14:09:40Z |
dc.date.available.fl_str_mv |
2021-03-09T14:09:40Z |
dc.date.issued.fl_str_mv |
2021 |
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 |
GRANJA, Marcelo Gomes et al. Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life. Journal of Neuroinflammation, v. 18, n. 60, 18p, 2021. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/46312 |
dc.identifier.issn.pt_BR.fl_str_mv |
1178-7031 |
dc.identifier.doi.none.fl_str_mv |
10.1186/s12974-021-02106-1 |
identifier_str_mv |
GRANJA, Marcelo Gomes et al. Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life. Journal of Neuroinflammation, v. 18, n. 60, 18p, 2021. 1178-7031 10.1186/s12974-021-02106-1 |
url |
https://www.arca.fiocruz.br/handle/icict/46312 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
Dove Press |
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Dove Press |
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