RT info:eu-repo/semantics/article T1 Long-term effects of low doses of Chlorpyrifos exposure at the preweaning developmental stage: A locomotor, pharmacological, brain gene expression and gut microbiome analysis A1 Pérez Fernández, Cristian A1 Morales Navas, Miguel A1 Guardia Escote, Laia A1 Garrido Cárdenas, José Antonio A1 Colomina, María Teresa A1 Giménez, Estela A1 Sánchez Santed, Fernando K1 Chlorpyrifos K1 Locomotor K1 Cholinergic system K1 GABAergic system K1 Gene expression K1 Gut microbiome K1 Fisiología K1 Physiology K1 Biología molecular K1 Molecular biology AB Development is especially sensitive to Chlorpyrifos (CPF) toxicity, associated with several neurodegenerativeand neurodevelopmental disorders where motor function dysfunction is a core symptom. Amongst the alternative molecular targets to cholinesterases inhibition, developmental CPF alters different components in themost important neurotransmitter systems, although this depends on the exposure period. Exposure during thelate postnatal preweaning stage is the least studied by far. This period includes essential neurodevelopmentalprocesses and has an important translational meaning. The present study analyzed the influence of low doses ofCPF on this developmental window on locomotor activity and the state of the different neurotransmitter systemsby pharmacological challenges. Brain gene expression and microbiome modulation following CPF were alsoanalyzed. CPF exposure long-term increased spontaneous vertical activity, female's activity following acutestress, hyposensitized the cholinergic system and hypersensitized the GABAergic system, up-regulated bothmuscarinic 2 receptor and GABA-A-α2 receptor subunit in the dorsal striatum and the frontal cortex, respectivelyand induced gut microbiota dysbiosis at both genus and species levels. The present study supports alternativemolecular targets than the ChEs following late postnatal, preweaning exposure to low doses of CPF, focusing onboth cholinergic and GABAergic systems and the gut microbiome as an important factor. PB Elsevier SN 0278-6915 YR 2020 FD 2020-01 LK http://hdl.handle.net/10259/8632 UL http://hdl.handle.net/10259/8632 LA eng NO This study was supported by two grants from the Ministerio de Economía y Competitividad, Spanish Government and the Fondo Europeo de Desarrollo Regional (MINECO-FEDER). Grant numbers: PSI2017-86847-C2-1-R MINECO-FEDER and PSI2017-86847-C2-2-R. DS Repositorio Institucional de la Universidad de Burgos RD 17-jul-2024