Neonatal exposure to ultrafine iron but not combined iron and sulfur aerosols recapitulates air pollution-induced impulsivity in mice

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Air pollution (AP) is becoming recognized as a major threat to neurological health across the lifespan with increased risk of both neurodevelopmental and neurodegenerative disorders. AP is a complex mixture of gases and particulate matter, with adsorbed contaminants including metals and trace elements, which may differentially contribute to its neurodevelopmental impacts. Iron (Fe) is one of the most abundant metals found in AP, and Fe concentrations may drive some behavioral deficits observed in children. Furthermore, brains of neonate mice exposed to concentrated ambient ultrafine particulate matter (UFP) show significant brain accumulation of Fe and sulfur (S) supporting the hypothesis that AP exposure may lead to brain metal dyshomeostasis. The current study determined the extent to which behavioral effects of UFP, namely memory deficits and impulsive-like behavior, could be recapitulated with exposure to Fe aerosols with or without concomitant SO2. Male and female neonate mice were either exposed to filtered air or spark discharge-generated ultrafine Fe particles with or without SO2 gas (n = 12/exposure/sex). Inhalation exposures occurred from postnatal day (PND) 4–7 and 10–13 for 4 hr/day, mirroring our previous UFP exposures. Mice were aged to adulthood prior to behavioral testing. While Fe or Fe + SO2 exposure did not affect gross locomotor behavior, Fe + SO2-exposed females displayed consistent thigmotaxis during locomotor testing. Neither exposure affected novel object memory. Fe or Fe + SO2 exposure produced differential outcomes on a fixed-interval reinforcement schedule with males showing higher (Fe-only) or lower (Fe + SO2) response rates and postreinforcement pauses (PRP) and females showing higher (Fe-only) PRP. Lastly, Fe-exposed, but not Fe + SO2-exposed, males showed increased impulsive-like behavior in tasks requiring response inhibition with no such effects in female mice. These findings suggest that: 1) exposure to realistic concentrations of Fe aerosols can recapitulate behavioral effects of UFP exposure, 2) the presence of SO2 can modulate behavioral effects of Fe inhalation, and 3) brain metal dyshomeostasis may be an important factor in AP neurotoxicity.