Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice

Detalhes bibliográficos
Autor(a) principal: Castilo, Ingrid Del
Data de Publicação: 2022
Outros Autores: 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.
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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spelling 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
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv MDPI
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dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/55015/2/AmandaRego_FlavioLara_etal_IOC_2022.pdf
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