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

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Autor(es): dc.contributorUniversidade Federal do Rio de Janeiro (UFRJ)-
Autor(es): dc.contributorUniversidade Federal do Rio Grande do Sul-
Autor(es): dc.contributorFundação Oswaldo Cruz-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorCastilo, Ingrid del-
Autor(es): dc.creatorNeumann, Arthur S.-
Autor(es): dc.creatorLemos, Felipe S.-
Autor(es): dc.creatorBastiani, Marco A. de-
Autor(es): dc.creatorOliveira, Felipe L.-
Autor(es): dc.creatorZimmer, Eduardo R.-
Autor(es): dc.creatorRêgo, Amanda M.-
Autor(es): dc.creatorHardoim, Cristiane C. P.-
Autor(es): dc.creatorAntunes, Luis Caetano M.-
Autor(es): dc.creatorLara, Flávio A.-
Autor(es): dc.creatorFigueiredo, Claudia P.-
Autor(es): dc.creatorClarke, Julia R.-
Data de aceite: dc.date.accessioned2025-08-21T21:04:12Z-
Data de disponibilização: dc.date.available2025-08-21T21:04:12Z-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2022-05-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/ijms23105583-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/240066-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/240066-
Descrição: dc.descriptionRoundUp® (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 GBH-RUp 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.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionFaculdade de Farmácia Universidade Federal do Rio de Janeiro, RJ-
Descrição: dc.descriptionInstituto de Ciências Biomédicas Universidade Federal do Rio de Janeiro, RJ-
Descrição: dc.descriptionDepartamento de Farmacologia Universidade Federal do Rio Grande do Sul, RS-
Descrição: dc.descriptionInstituto Oswaldo Cruz Fundação Oswaldo Cruz, RJ-
Descrição: dc.descriptionInstituto de Biociências Universidade Estadual Paulista, SP-
Descrição: dc.descriptionInstituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas Centro de Desenvolvimento Tecnológico em Saúde Fundação Oswaldo Cruz, RJ-
Descrição: dc.descriptionInstituto de Biociências Universidade Estadual Paulista, SP-
Descrição: dc.descriptionCAPES: 001-
Descrição: dc.descriptionFAPESP: 2016/17189-7-
Descrição: dc.descriptionCNPq: 303843/2017-9-
Descrição: dc.descriptionCNPq: 305511/2018-1-
Idioma: dc.languageen-
Relação: dc.relationInternational Journal of Molecular Sciences-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectgut–brain axis-
Palavras-chave: dc.subjectherbicide-
Palavras-chave: dc.subjectinflammation-
Palavras-chave: dc.subjectneurodevelopmental diseases-
Palavras-chave: dc.subjectrepetitive behavior-
Palavras-chave: dc.subjectsocial impairment-
Título: dc.titleLifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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