Maternal Stress and Effects of Prenatal Air Pollution on Offspring Mental Health Outcomes in Mice

Background: Low socioeconomic status is consistently associated with reduced physical and -mental health, but the mechanisms remain unclear. Increased levels of urban air pollutants interacting with parental stress have been proposed to explain health disparities in respiratory disease, but the impact of such interactions on mental health is unknown. Objectives: We aimed to determine whether prenatal air pollution exposure and stress during pregnancy act synergistically on offspring to induce a neuroinflammatory response and subsequent neuro-cognitive disorders in adulthood. Methods: Mouse dams were intermittently exposed via oropharyngeal aspiration to diesel exhaust particles (DEP; 50 mu g x 6 doses) or vehicle throughout gestation. This exposure was combined with standard housing or nest material restriction (NR; a novel model of maternal stress) during the last third of gestation. Results: Adult (postnatal day 60) offspring of dams that experienced both stressors (DEP and NR) displayed increased anxiety, but only male offspring of this group had impaired cognition. Furthermore, maternal DEP exposure increased pro-inflammatory interleukin (IL)-1 beta levels within the brains of adult males but not females, and maternal DEP and NR both decreased anti-inflammatory IL-10 in male, but not female, brains. Similarly, only DEP/NR males showed increased expression of the innate immune recognition gene toll-like receptor 4 (Tlr4) and its downstream effector, caspase-1. Conclusions: These results show that maternal stress during late gestation increases the susceptibility of offspring-particularly males-to the deleterious effects of pre-natal air pollutant exposure, which may be due to a synergism of these factors acting on innate immune recognition genes and downstream neuroinflammatory cascades within the developing brain.