Developmental Ambient Air Pollution Exposure in Mice Alters Fronto-Striatal Neurotransmitter System Function: Male-Biased Serotonergic Vulnerability

Abstract

Air pollution (AP) exposures have been associated with autism (ASD), schizophrenia (SCZ), and attention deficit hyperactivity disorder (ADHD), male-biased neurodevelopmental disorders that are linked to alterations in brain fronto-striatal neurotransmitter systems. The current study sought to assess how developmental exposures of mice to inhaled ambient ultrafine particle (UFP) air pollution, considered its most reactive component, alters fronto-striatal functional correlations. Mice were exposed via inhalation to concentrated ambient UFPs from postnatal days (PND) 4–7 and 10–13. Frontal cortex, striatum, and serum were collected at PND14 and PND50 to evaluate both acute and persistent effects. UFP-induced changes, more extensive and persistent in males, included elimination of frontal cortical kynurenine correlations with striatal neurotransmitter function, persistent immunosuppression of approximately 50%, and striatal neurotransmitter turnover correlations with serum corticosterone. More limited effects in females did not show persistence. Collectively, these findings depict an apparently physiologically-integrated UFP-induced persistent male-biased vulnerability to brain fronto-striatal system dysfunction that could contribute to behavioral deficits associated with neurodevelopmental disorders. Further studies are needed to ascertain the interactive physiological mechanisms of male fronto-striatal vulnerability and their relation to behavioral impairments, mechanisms of apparent female compensation, and specific contaminants of AP that underlie this vulnerability.