Metabolomics analysis explores the rescue to neurobehavioral disorder induced by maternal PM_2.5 exposure in mice

Reproductive epidemiological studies have suggested associations between perinatal exposure to fine particulate matter (PM_2.5) and adverse birth outcomes. To explore the effects of early prenatal exposure to PM_2.5 on subsequent generations, pregnant mice were exposed to PM_2.5 or filtered clean air in whole body dynamic exposure chambers for 14 consecutive days from gestation day (GD) 1.5 to GD15.5. Neurobehavioral tests showed that spontaneous locomotion and exploratory behaviors in the offspring were significantly enhanced in the open field test. Meanwhile, metabolomics analysis suggested activation of dopamine pathway while inhibition of glycine pathway in murine brains. Administration of the DRD4 antagonist, clozapine; or supplementation of glycine receptor agonist, taurine, to mice offspring attenuated the locomotor hyperactivities to levels indistinguishable from controls. These data provide strong evidence that maternal exposure to air pollution might increase the risk for neural disorders in the offspring during critical periods of brain development.