Medium and long-term effects of low doses of Chlorpyrifos during the postnatal, preweaning developmental stage on sociability, dominance, gut microbiota and plasma metabolites

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental pathology characterized by altered verbalizations, reduced social interaction behavior, and stereotypies. Environmental factors have been associated with its development. Some researchers have focused on pesticide exposure. Chlorpyrifos (CPF) is the most used Organophosphate. Previous developmental studies with CPF showed decreased, enhanced or no effect on social outcomes eminently in mice. The study of CPF exposure during preweaning stages on social behavior is sparse in mice and non-existent in rats. d stressors could be at the basis of ASD development, and around postnatal day 10 in the rat is equivalent to the human birthday in neurodevelopmental terms. We explored the effects of exposure to low doses (1mg/kg/mL/day) of CPF during this stage regarding: sociability, dominance gut microbiome and plasma metabolomic profile, since alterations in these systems have also been linked to ASD. There was a modest influence of CPF on social behavior in adulthood, with null effects during adolescence. Dominance and hierarchical status were not affected by exposure. Dominance status explained the significant reduction in reaction to social novelty observed on the sociability test. CPF induced a significant gut microbiome dysbiosis and triggered a hyperlipidemic, hypoglycemic/hypogluconeogenesis and a general altered cell energy production in females. These behavioral results in rats extend and complement previous studies with mice and show novel influences on gut metagenomics and plasma lipid profile and metabolomics, but do not stablish a relation between the exposure to CPF and the ASD phenotype. The effects of dominance status on reaction to social novelty have an important methodological meaning for future research on sociability.