Life-long Dietary Pesticide Cocktail Induces Astrogliosis Along with Behavioral Adaptations and Activates p450 Metabolic Pathways

Autor: Laila Mselli-Lakhal, Laurence Gamet-Payrastre, Etienne Audinat, Nicola Marchi, Jean-Marc Pascussi, Frédéric de Bock, Wendy Klement, Fabiana Oliviero, Frédéric Lasserre, Giuseppe Gangarossa, Tangui Maurice, Sandrine Ellero-Simatos, Emma Zub, Isabel Forner-Piquer, Marine Blaquière
Přispěvatelé: CCSD, Accord Elsevier, Mélange de pesticides et axe foie-cerveau : implication des récepteurs aux xénobiotiques - - HepatoBrain2017 - ANR-17-CE34-0005 - AAPG2017 - VALID, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Mécanismes moléculaires dans les démences neurodégénératives (MMDN), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), This work was support by ANR-Hepatobrain, ANSES Epidemicmac, MUSE-iSite University of Montpellier., ANR-17-CE34-0005,HepatoBrain,Mélange de pesticides et axe foie-cerveau : implication des récepteurs aux xénobiotiques(2017), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)
Rok vydání: 2020
Předmět:
0301 basic medicine
Tolerable daily intake
Male
medicine.medical_specialty
[SDV]Life Sciences [q-bio]
Biology
Hippocampal formation
memory
03 medical and health sciences
Mice
0302 clinical medicine
Growth factor receptor
Downregulation and upregulation
Internal medicine
medicine
Weaning
[SDV.EE.SANT] Life Sciences [q-bio]/Ecology
environment/Health
Animals
Gliosis
detoxification
Pesticides
[SDV.EE]Life Sciences [q-bio]/Ecology
environment
[SDV.EE.SANT]Life Sciences [q-bio]/Ecology
environment/Health
behavior
General Neuroscience
astrocytes
P450 enzymes
Pesticide
medicine.disease
3. Good health
Astrogliosis
Diet
[SDV] Life Sciences [q-bio]
Mice
Inbred C57BL
[SDV.EE] Life Sciences [q-bio]/Ecology
environment
030104 developmental biology
Endocrinology
ACOX1
Female
metabolism
030217 neurology & neurosurgery
electroencephalography
Metabolic Networks and Pathways
pesticides cocktail
Zdroj: Neuroscience
Neuroscience, 2020, 446, pp.225_237. ⟨10.1016/j.neuroscience.2020.07.039⟩
Neuroscience, Elsevier-International Brain Research Organization, 2020, 446, pp.225_237. ⟨10.1016/j.neuroscience.2020.07.039⟩
ISSN: 1873-7544
0306-4522
Popis: International audience; Exposure to environmental contaminants is a public health concern. However, pre-clinical studies examining the impact of pesticides at low-dose and their long-term consequences are uncommon. Here, C57BL6/j male and female mice were daily fed from weaning and up to 12 months, corresponding to early-childhood into middle-age in humans, using chow pellets containing a cocktail of pesticides and exposing them to the tolerable daily intake level for each pesticide. We found that 12 months of dietary exposure to pesticides was associated with a moderate astrogliosis in the hippocampus. The expression of platelet-derived growth factor receptor beta (PDGFRβ), an indicator of pro-fibrotic tissue changes, was modified at the perivascular level. Examination of Iba1+ microglial cells did not reveal sizeable changes. Concomitantly to astrogliosis, spontaneous spatial memory and sociability were impaired in males at 12 months of dietary exposure to pesticides. Telemetry electrocorticograhic explorations ruled out the presence of epileptiform activity or theta-gamma wave modifications in these conditions. Long-term pesticides impacted the periphery where the hepatic P450 metabolic cytochromes Cyp4a14 and Cyp4a10 were significantly upregulated in male and female mice during the 12 months of exposure. The expression of β-oxidation genes, such as Acox1, Cpt1a and Eci, was also significantly increased in male and female mice in response to pesticides. Collectively, our results indicate that long-term exposure to pesticides cocktail elicits spatio-temporally restricted brain modifications and significant activation of P450 pathways in the periphery. These brain-peripheral adjustments are discussed as time-dependent vulnerability elements.
Databáze: OpenAIRE
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