Maternal exposure of mice to glyphosate induces depression- and anxiety-like behavior in the offspring via alterations of the gut-brain axis.

Autor: Buchenauer L; Helmholtz Centre for Environmental Research - UFZ, Department of Environmental Immunology, Leipzig, Germany; University of Leipzig, Leipzig University Medical Center, Department of Dermatology, Venerology and Allergology, Leipzig, Germany., Haange SB; Helmholtz Centre for Environmental Research - UFZ, Department of Molecular Systems Biology, Leipzig, Germany., Bauer M; Helmholtz Centre for Environmental Research - UFZ, Department of Environmental Immunology, Leipzig, Germany., Rolle-Kampczyk UE; Helmholtz Centre for Environmental Research - UFZ, Department of Molecular Systems Biology, Leipzig, Germany., Wagner M; Helmholtz Centre for Environmental Research - UFZ, Department of Environmental Immunology, Leipzig, Germany; University of Leipzig, Leipzig University Medical Center, Department of Dermatology, Venerology and Allergology, Leipzig, Germany., Stucke J; Helmholtz Centre for Environmental Research - UFZ, Department of Environmental Immunology, Leipzig, Germany; University of Leipzig, Leipzig University Medical Center, Department of Dermatology, Venerology and Allergology, Leipzig, Germany., Elter E; Helmholtz Centre for Environmental Research - UFZ, Department of Environmental Immunology, Leipzig, Germany; University of Leipzig, Leipzig University Medical Center, Department of Dermatology, Venerology and Allergology, Leipzig, Germany., Fink B; Helmholtz Centre for Environmental Research - UFZ, Department of Environmental Immunology, Leipzig, Germany., Vass M; University of Leipzig, Leipzig University Medical Center, Department of Dermatology, Venerology and Allergology, Leipzig, Germany., von Bergen M; Helmholtz Centre for Environmental Research - UFZ, Department of Molecular Systems Biology, Leipzig, Germany; University of Leipzig, Faculty of Life Sciences, Institute of Biochemistry, Leipzig, Germany; German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, Germany., Schulz A; University of Leipzig, Medical Faculty, Rudolf Schönheimer Institute of Biochemistry, Leipzig, Germany., Zenclussen AC; Helmholtz Centre for Environmental Research - UFZ, Department of Environmental Immunology, Leipzig, Germany; Perinatal Immunology, Saxonian Incubator for Clinical Translation (SIKT), Medical Faculty, University Leipzig, 04103 Leipzig, Germany., Junge KM; Helmholtz Centre for Environmental Research - UFZ, Department of Environmental Immunology, Leipzig, Germany; AKAD University Stuttgart, School of Health and Social Sciences, Stuttgart, Germany., Stangl GI; Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany., Polte T; Helmholtz Centre for Environmental Research - UFZ, Department of Environmental Immunology, Leipzig, Germany; University of Leipzig, Leipzig University Medical Center, Department of Dermatology, Venerology and Allergology, Leipzig, Germany. Electronic address: tobias.polte@ufz.de.
Jazyk: angličtina
Zdroj: The Science of the total environment [Sci Total Environ] 2023 Dec 20; Vol. 905, pp. 167034. Date of Electronic Publication: 2023 Sep 12.
DOI: 10.1016/j.scitotenv.2023.167034
Abstrakt: The past decade has been characterized by increased awareness and de-stigmatization of mental health issues, in particular the most common neuropsychiatric disorders depression and anxiety. Further, with growing understanding of neurodevelopmental disorders such as attention deficit and hyperactivity disorder and autism spectrum disorder, the number of diagnosed patients has increased. The pathogenesis of these behavioral disorders is multifactorial and early-life exposure to environmental chemicals has been proposed to be a relevant risk factor that might mediate these effects by disturbances on the gut-brain-axis. However, for glyphosate, the most widely used pesticide worldwide, there are only limited and inconsistent findings that link chronic low-dose exposure in particular during early life to neurobehavioral disorders. Here, we explored the impact of maternal oral glyphosate exposure (0.5 and 50 mg/kg body weight/day) during pregnancy and the lactational period on offspring's behavior, brain gene expression and gut microbiota using a cross-generational mouse model. Behavioral analyses revealed a depression- and anxiety-like behavior as well as social deficits most notably in adult female offspring of glyphosate-exposed dams. Furthermore, the expression of tryptophan hydroxylase 2, an enzyme discussed to be linked to behavioral problems, was reduced in the hippocampus of female offspring and correlated to a glyphosate-induced DNA hypermethylation of the gene. Moreover, maternal glyphosate exposure significantly altered the gut microbiota in the female offspring including a decreased abundance of Akkermansia and increased abundance of Alistipes and Blautia, bacteria involved in tryptophan metabolism and associated with depression- and anxiety-like disorders. Our results suggest that glyphosate might influence the gut-brain axis crosstalk following in-utero and lactational exposure. This study underlines the importance of understanding the impact of exposure to pesticides on the gut-brain axis and further emphasizes the need for microbiome analyses to be compulsorily included in health risk assessments of pesticides.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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