Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice
Autor(a) principal: | |
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Data de Publicação: | 2022 |
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/55015 |
Resumo: | Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil. |
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Castilo, Ingrid DelNeumann, Arthur S.Lemos, Felipe S.Bastiani, Marco A. DeOliveira, Felipe L.Zimmer, Eduardo R.Rêgo, Amanda M.Hardoim, Cristiane C. P.Antunes, Luis Caetano M.Lara, Flávio A.Figueiredo, Claudia P.Clarke, Julia R.2022-10-06T14:04:47Z2022-10-06T14:04:47Z2022CASTILO, Ingrid Del et al. Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice. International Journal of Molecular Sciences, v. 23, 5583, p. 1 - 17, May 2022.1422-0067https://www.arca.fiocruz.br/handle/icict/5501510.3390/ijms23105583engMDPIHerbicidaComportamento repetitivoDeficiência socialDoenças do neurodesenvolvimentoEixo intestino-cérebroInflamaçãoHerbicideRepetitive behaviorSocial impairmentNeurodevelopmental diseasesGut–brain axisInflammationLifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Faculdade 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 Ciências Biomédicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio Grande do Sul. Departamento de Farmacologia. Porto Alegre, RS, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio Grande do Sul. Departamento de Farmacologia. Porto Alegre, RS, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Universidade Estadual Paulista. Instituto de Biociências. São Vicente, SP Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade 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. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil.RoundUp® (RUp) is a comercial formulation containing glyphosate (N-(phosphono-methyl) glycine), and is the world’s leading wide-spectrum herbicide used in agriculture. Supporters of the broad use of glyphosate-based herbicides (GBH) claim they are innocuous to humans, since the active compound acts on the inhibition of enzymes which are absent in human cells. However, the neurotoxic effects of GBH have already been shown in many animal models. Further, these formulations were shown to disrupt the microbiome of different species. Here, we investigated the effects of a lifelong exposure to low doses of the GBH-RUp on the gut environment, including morphological and microbiome changes. We also aimed to determine whether exposure to GBH-RUp could harm the developing brain and lead to behavioral changes in adult mice. To this end, animals were exposed to GBH-RUp in drinking water from pregnancy to adulthood. GBH-RUp-exposed mice had no changes in cognitive function, but developed impaired social behavior and increased repetitive behavior. GBH-Rup-exposed mice also showed an activation of phagocytic cells (Iba-1–positive) in the cortical brain tissue. GBH-RUp exposure caused increased mucus production and the infiltration of plama cells (CD138-positive), with a reduction in phagocytic cells. Long-term exposure to GBHRUp also induced changes in intestinal integrity, as demonstrated by the altered expression of tight junction effector proteins (ZO-1 and ZO-2) and a change in the distribution of syndecan-1 proteoglycan. The herbicide also led to changes in the gut microbiome composition, which is also crucial for the establishment of the intestinal barrier. Altogether, our findings suggest that long-term GBH-RUp exposure leads to morphological and functional changes in the gut, which correlate with behavioral changes that are similar to those observed in patients with neurodevelopmental disorders.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALAmandaRego_FlavioLara_etal_IOC_2022.pdfAmandaRego_FlavioLara_etal_IOC_2022.pdfapplication/pdf4364757https://www.arca.fiocruz.br/bitstream/icict/55015/2/AmandaRego_FlavioLara_etal_IOC_2022.pdf7a2491f20ee7b394b855545f060eaa64MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/55015/1/license.txt5a560609d32a3863062d77ff32785d58MD51icict/550152023-09-04 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dc.title.en_US.fl_str_mv |
Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice |
title |
Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice |
spellingShingle |
Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice Castilo, Ingrid Del Herbicida Comportamento repetitivo Deficiência social Doenças do neurodesenvolvimento Eixo intestino-cérebro Inflamação Herbicide Repetitive behavior Social impairment Neurodevelopmental diseases Gut–brain axis Inflammation |
title_short |
Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice |
title_full |
Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice |
title_fullStr |
Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice |
title_full_unstemmed |
Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice |
title_sort |
Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice |
author |
Castilo, Ingrid Del |
author_facet |
Castilo, Ingrid Del Neumann, Arthur S. Lemos, Felipe S. Bastiani, Marco A. De Oliveira, Felipe L. Zimmer, Eduardo R. Rêgo, Amanda M. Hardoim, Cristiane C. P. Antunes, Luis Caetano M. Lara, Flávio A. Figueiredo, Claudia P. Clarke, Julia R. |
author_role |
author |
author2 |
Neumann, Arthur S. Lemos, Felipe S. Bastiani, Marco A. De Oliveira, Felipe L. Zimmer, Eduardo R. Rêgo, Amanda M. Hardoim, Cristiane C. P. Antunes, Luis Caetano M. Lara, Flávio A. Figueiredo, Claudia P. Clarke, Julia R. |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Castilo, Ingrid Del Neumann, Arthur S. Lemos, Felipe S. Bastiani, Marco A. De Oliveira, Felipe L. Zimmer, Eduardo R. Rêgo, Amanda M. Hardoim, Cristiane C. P. Antunes, Luis Caetano M. Lara, Flávio A. Figueiredo, Claudia P. Clarke, Julia R. |
dc.subject.other.en_US.fl_str_mv |
Herbicida Comportamento repetitivo Deficiência social Doenças do neurodesenvolvimento Eixo intestino-cérebro Inflamação |
topic |
Herbicida Comportamento repetitivo Deficiência social Doenças do neurodesenvolvimento Eixo intestino-cérebro Inflamação Herbicide Repetitive behavior Social impairment Neurodevelopmental diseases Gut–brain axis Inflammation |
dc.subject.en.en_US.fl_str_mv |
Herbicide Repetitive behavior Social impairment Neurodevelopmental diseases Gut–brain axis Inflammation |
description |
Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-10-06T14:04:47Z |
dc.date.available.fl_str_mv |
2022-10-06T14:04:47Z |
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 |
CASTILO, Ingrid Del et al. Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice. International Journal of Molecular Sciences, v. 23, 5583, p. 1 - 17, May 2022. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/55015 |
dc.identifier.issn.en_US.fl_str_mv |
1422-0067 |
dc.identifier.doi.none.fl_str_mv |
10.3390/ijms23105583 |
identifier_str_mv |
CASTILO, Ingrid Del et al. Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice. International Journal of Molecular Sciences, v. 23, 5583, p. 1 - 17, May 2022. 1422-0067 10.3390/ijms23105583 |
url |
https://www.arca.fiocruz.br/handle/icict/55015 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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MDPI |
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MDPI |
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