48 Brain neurotransmitter changes following gestational exposures of mice to ambient air pollution: modulation by sex, behavioural experience and life stage

Abstract Human studies have linked air pollution (AP) to multiple neurodevelopmental disorders as well as to multiple neurodegenerative diseases and disorders, all conditions with increasing global prevalence that are subserved by broad underlying brain neurotransmitter dysregulation. Currently undetermined are the critical periods of AP exposures associated with such consequences and the potential for a subsequent trajectory of effects at different life stages and in response to different conditions and physiological demands. To further this understanding, pregnant mice were inhalationally exposed to concentrated ambient ultrafine particle air pollution for 4 hr/day from gestational day 0.5 to 16.5 with changes in frontal cortex and striatal neurotransmitter levels and frontostriatal correlations in offspring assessed at postnatal day (PND) 14, 41, 62 and 418, with the last time point derived from mice with and without behavioural experience. Predominant effects in females emerged after adolescence (PND62) with reductions in both frontal cortex and striatum in all three classes of neurotransmitters. In males, onset of adolescence (PND41) was accompanied by reductions in both glutamatergic and serotonergic neurotransmitter classes. In both sexes, the dynamic increases in neurotransmitters required by behavioural experience (PND418 Beh) were not evident in female frontal cortex serotonergic neurotransmitters and in male frontal cortex in all three classes of neurotransmitter systems. Collectively, this trajectory of effects underscores the persistence of developmental AP exposures and the importance of context, including sex, brain region and life stage in later emergent consequences, such that reliance on a single time point/condition may be misleading.