Developmental exposure to terbutaline alters cell signaling in mature rat brain regions and augments the effects of subsequent neonatal exposure to the organophosphorus insecticide chlorpyrifos

摘要: Exposure to apparently unrelated neurotoxicants can nevertheless converge on common neurodevelopmental events. We examined the long-term effects of developmental exposure rats terbutaline, a beta-adrenoceptor agonist used arrest preterm labor, and organophosphorus insecticide chlorpyrifos (CPF) separately together. Treatments mimicked appropriate stages for human exposures: terbutaline postnatal days (PN) 2-5 CPF PN11-14, with assessments conducted PN45. Although neither treatment affected growth or viability, each elicited alterations in CNS cell signaling mediated by adenylyl cyclase (AC), transduction pathway shared numerous neuronal hormonal signals. Terbutaline altered brainstem cerebellum, gender differences particularly notable cerebellum (enhanced AC males, suppressed females). By itself, deficits midbrain, brainstem, striatum. However, sequential followed produced larger involved wider spectrum brain regions than were obtained either agent alone. In cerebral cortex, adverse combined intensified between PN45 PN60, suggesting that exposures alter program development synaptic communication, leading emerge even after adolescence. These findings indicate like CPF, is neurotoxicant, reinforce idea its use labor may create subpopulation sensitized insecticides.