| Author | Castilo, Ingrid Del | |
| Author | Neumann, Arthur S. | |
| Author | Lemos, Felipe S. | |
| Author | Bastiani, Marco A. De | |
| Author | Oliveira, Felipe L. | |
| Author | Zimmer, Eduardo R. | |
| Author | Rêgo, Amanda M. | |
| Author | Hardoim, Cristiane C. P. | |
| Author | Antunes, Luis Caetano M. | |
| Author | Lara, Flávio A. | |
| Author | Figueiredo, Claudia P. | |
| Author | Clarke, Julia R. | |
| Access date | 2022-10-06T14:04:47Z | |
| Available date | 2022-10-06T14:04:47Z | |
| Document date | 2022 | |
| Citation | 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. | en_US |
| ISSN | 1422-0067 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/55015 | |
| Language | eng | en_US |
| Publisher | MDPI | en_US |
| Rights | open access | |
| Subject in Portuguese | Herbicida | en_US |
| Subject in Portuguese | Comportamento repetitivo | en_US |
| Subject in Portuguese | Deficiência social | en_US |
| Subject in Portuguese | Doenças do neurodesenvolvimento | en_US |
| Subject in Portuguese | Eixo intestino-cérebro | en_US |
| Subject in Portuguese | Inflamação | en_US |
| Title | Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice | en_US |
| Type | Article | |
| DOI | 10.3390/ijms23105583 | |
| Abstract | 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. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio Grande do Sul. Departamento de Farmacologia. Porto Alegre, RS, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio Grande do Sul. Departamento de Farmacologia. Porto Alegre, RS, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Estadual Paulista. Instituto de Biociências. São Vicente, SP Brasil. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Subject | Herbicide | en_US |
| Subject | Repetitive behavior | en_US |
| Subject | Social impairment | en_US |
| Subject | Neurodevelopmental diseases | en_US |
| Subject | Gut–brain axis | en_US |
| Subject | Inflammation | en_US |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
