Long-term effects of low doses of Chlorpyrifos exposure at the preweaning developmental stage: A locomotor, pharmacological, brain gene expression and gut microbiome analysis

Development is especially sensitive to Chlorpyrifos (CPF) toxicity, associated with several neurodegenerative and neurodevelopmental disorders where motor function dysfunction is a core symptom. Amongst the alternative molecular targets to cholinesterases inhibition, developmental CPF alters differe...

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Veröffentlicht in:Food and chemical toxicology 2020-01, Vol.135, p.110865-110865, Article 110865
Hauptverfasser: Perez-Fernandez, Cristian, Morales-Navas, Miguel, Guardia-Escote, Laia, Garrido-Cárdenas, José Antonio, Colomina, María Teresa, Giménez, Estela, Sánchez-Santed, Fernando
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Sprache:eng
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Zusammenfassung:Development is especially sensitive to Chlorpyrifos (CPF) toxicity, associated with several neurodegenerative and neurodevelopmental disorders where motor function dysfunction is a core symptom. Amongst the alternative molecular targets to cholinesterases inhibition, developmental CPF alters different components in the most important neurotransmitter systems, although this depends on the exposure period. Exposure during the late postnatal preweaning stage is the least studied by far. This period includes essential neurodevelopmental processes and has an important translational meaning. The present study analyzed the influence of low doses of CPF on this developmental window on locomotor activity and the state of the different neurotransmitter systems by pharmacological challenges. Brain gene expression and microbiome modulation following CPF were also analyzed. CPF exposure long-term increased spontaneous vertical activity, female's activity following acute stress, hyposensitized the cholinergic system and hypersensitized the GABAergic system, up-regulated both muscarinic 2 receptor and GABA-A-α2 receptor subunit in the dorsal striatum and the frontal cortex, respectively and induced gut microbiota dysbiosis at both genus and species levels. The present study supports alternative molecular targets than the ChEs following late postnatal, preweaning exposure to low doses of CPF, focusing on both cholinergic and GABAergic systems and the gut microbiome as an important factor. •Late postnatal CPF exposure long-term triggered spontaneous hyper motricity and stress-induced hyper motricity (females).•Late postnatal CPF exposure long-term hypo/hyper-sensitized the cholinergic system and the GABAergic system, respectively.•Late postnatal CPF exposure long-term up-regulated m2 receptor (dorsal striatum) and GABA-A-α2 subunit (frontal cortex).•Late postnatal CPF exposure long-term induced gut microbiota dysbiosis at both genus and species levels.
ISSN:0278-6915
1873-6351
DOI:10.1016/j.fct.2019.110865