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A subchronic low-dose exposure of a glyphosate-based herbicide induces depressive and anxious-like behavior in mice: quercetin therapeutic approach

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Abstract

In this study, we investigated the possible role of pesticide exposure in contributing to neurological diseases such as depression. Here, we evaluated whether a subchronic low dose of a glyphosate-based herbicide (GBH) could induce alterations in the central nervous system, using the flavonoid quercetin as a therapeutic strategy. Forty mice were divided into four treatment groups: control, GBH, quercetin, and GBH+Quer groups and received 50 mg/kg of GBH solution, 30 mg/kg of quercetin, and/or vehicles for 30 days via gavage. After performing behavioral tests, such as the open field (OF), elevated plus maze (EPM), forced swim test (FST), and sucrose preference test (SPT), the mice were euthanized and their hippocampal tissues were collected to measure the levels of oxidative stress markers such as reactive species (RS), total antioxidant capacity (FRAP), reduced glutathione (GSH), and acetylcholinesterase activity (AChE), as well as for histological evaluation. The GBH group showed anxious and depressive-like behavior in the EPM and FST tests, as well as increased levels of RS and decreased GSH levels in the hippocampus. Quercetin treatment in the GBH+Quer group allowed partial or total improvement in behavioral tests (EPM and FST) and in the levels of oxidative stress markers (RS and GSH). However, the quercetin group showed similar behavior to the GBH group after treatment. The results revealed that oral exposure to a subchronic low dose of GBH was capable of promoting effects on behavior and oxidative stress in the hippocampus of mice. In addition, despite quercetin having a neuroprotective role, caution is needed when considering the possible per se effects of its continuous supplementation.

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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The National Council for Scientific and Technological Development–CNPQ is acknowledged for financial support to F. W. S. C., and FAPERGS are acknowledged for financial support to J. B. R. (Dr. Fellowships).

Funding

The present study had financial support by the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior–Brasil (CAPES)–Finance Code 001, the National Council for Scientific and Technological Development–CNPQ, and Fundação de Amparo à Pesquisa do Rio Grande do Sul-FAPERGS.

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Contributions

All authors contributed for the study’s development. D. F. B. and F. W. S. C. participated on formulation and definition of research’s goals and procedures. Methodology, analyses, and processing data were performed by C. C. S., J. B. R., M. B. S., and D. F. B. Interpretation of data and writing were conducted by D. F. B. (original draft) and F. W. S. C. (review and editing) and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Francielli Weber Santos Cibin.

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All animal experiments in the current study are approved by the Animal Use Ethics Committee (CEUA) under the number protocol 029/2017 and in accordance with the Brazilian Council for Control of Animal Experimentation (CONCEA).

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The authors declare no competing interests.

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Responsible Editor: Mohamed M. Abdel-Daim

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Bicca, D.F., Spiazzi, C.C., Ramalho, J.B. et al. A subchronic low-dose exposure of a glyphosate-based herbicide induces depressive and anxious-like behavior in mice: quercetin therapeutic approach. Environ Sci Pollut Res 28, 67394–67403 (2021). https://doi.org/10.1007/s11356-021-15402-3

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  • DOI: https://doi.org/10.1007/s11356-021-15402-3

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