title: Prenatal exposure to urban air nanoparticles in mice causes altered neuronal differentiation and depression-like responses.
abstract: Emerging evidence suggests that excessive exposure to traffic-derived air pollution during pregnancy may increase the vulnerability to neurodevelopmental alterations that underlie a broad array of neuropsychiatric disorders. We present a mouse model for prenatal exposure to urban freeway nanoparticulate matter (nPM). In prior studies, we developed a model for adult rodent exposure to re-aerosolized urban nPM which caused inflammatory brain responses with altered neuronal glutamatergic functions. nPMs are collected continuously for one month from a local freeway and stored as an aqueous suspension, prior to re-aerosolization for exposure of mice under controlled dose and duration. This paradigm was used for a pilot study of prenatal nPM impact on neonatal neurons and adult behaviors. Adult C57BL/6J female mice were exposed to re-aerosolized nPM (350 µg/m(3)) or control filtered ambient air for 10 weeks (3×5 hour exposures per week), encompassing gestation and oocyte maturation prior to mating. Prenatal nPM did not alter litter size, pup weight, or postnatal growth. Neonatal cerebral cortex neurons at 24 hours in vitro showed impaired differentiation, with 50% reduction of stage 3 neurons with long neurites and correspondingly more undifferentiated neurons at Stages 0 and 1. Neuron number after 24 hours of culture was not altered by prenatal nPM exposure. Addition of exogenous nPM (2 µg/ml) to the cultures impaired pyramidal neuron Stage 3 differentiation by 60%. Adult males showed increased depression-like responses in the tail-suspension test, but not anxiety-related behaviors. These pilot data suggest that prenatal exposure to nPM can alter neuronal differentiation with gender-specific behavioral sequelae that may be relevant to human prenatal exposure to urban vehicular aerosols.
authors.affiliation: Davis School of Gerontology, USC, Los Angeles, California, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Davis
authors.forename: Marco
authors.initials: M
authors.lastname: Bortolato
authors.forename: Sean C
authors.initials: SC
authors.lastname: Godar
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Sander
authors.forename: Nahoko
authors.initials: N
authors.lastname: Iwata
authors.forename: Payam
authors.initials: P
authors.lastname: Pakbin
authors.forename: Jean C
authors.initials: JC
authors.lastname: Shih
authors.forename: Kiros
authors.initials: K
authors.lastname: Berhane
authors.forename: Rob
authors.initials: R
authors.lastname: McConnell
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.forename: Caleb E
authors.initials: CE
authors.lastname: Finch
authors.forename: Todd E
authors.initials: TE
authors.lastname: Morgan
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002947:Cities; D003866:Depressive Disorder / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000633:toxicity*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity; D010865:Pilot Projects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000503:physiopathology*
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D048031:JNK Mitogen-Activated Protein Kinases