Alterations in behavior and proteomics following perinatal agonism of GABA-gated chloride channels in Long Evans rats
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The period of neurodevelopment is vulnerable to various insults, including those produced by environmental compounds. Here we used prototypical neurotoxicants to explore both behavioral and molecular alterations that can occur following chemical exposure during development. Pregnant Long Evans rats were gavaged with emamectin benzoate (EB; 3.78 mg/kg in 5 mL/kg DI water) a positive allosteric modulator to GABA-gated chloride channels, or vehicle, from gestational day 6 to postnatal day (PND) 21. For proteomic experiments, pup region specific brain tissues were collected throughout the postnatal period of exposure (PND2, 8, 15, 22). Cortex and cerebellum samples were assessed using Orbitrap LC-MS and Proteome Discover software, and further analyzed in Ingenuity Pathway Analysis. Behaviors were assessed throughout the experimental period, starting as early as PND2 as well as into adulthood. Behavioral assays included pup righting, a modified functional observational battery, locomotor activity, novel object recognition, acoustic startle response, and the Morris water maze. Proteomic analyses showed that protein signatures for EB-treated rats differed by region, sex, and age, indicating alterations in neuronal signaling and neurodegeneration pathways emerging at later timepoints (PND15v22). EB-exposed offspring displayed altered ontogeny of locomotor activity, decreased startle response, and uncoordinated hindlimb movements that began in early postnatal weeks and persisted into adulthood. Overall, we observed both behavioral and proteomic alterations following perinatal EB exposure, which can aid in understanding how environmental compounds can impact neurodevelopment. Follow up measures include assessing EB treated animals for histopathology. This is an abstract does not necessarily reflect US EPA policy.