2026-06-08T23:09:42Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/86322025-01-23T01:05:15Zcom_10259_9895com_10259_3989com_10259.4_106com_10259_2604col_10259_9896

Long-term effects of low doses of Chlorpyrifos exposure at the preweaning developmental stage: A locomotor, pharmacological, brain gene expression and gut microbiome analysis Pérez Fernández, Cristian Morales Navas, Miguel Guardia Escote, Laia Garrido Cárdenas, José Antonio Colomina, María Teresa Giménez, Estela Sánchez Santed, Fernando Chlorpyrifos Locomotor Cholinergic system GABAergic system Gene expression Gut microbiome 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. 2024-02-08T11:31:10Z 2024-02-08T11:31:10Z 2020-01 info:eu-repo/semantics/article 0278-6915 http://hdl.handle.net/10259/8632 10.1016/j.fct.2019.110865 eng Food and Chemical Toxicology. 2020, V. 135, 110865 https://doi.org/10.1016/j.fct.2019.110865 http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier