title: Neuropathological Consequences of Gestational Exposure to Concentrated Ambient Fine and Ultrafine Particles in the Mouse.
abstract: Increasing evidence indicates that the central nervous system (CNS) is a target of air pollution. We previously reported that postnatal exposure of mice to concentrated ambient ultrafine particles (UFP; ≤100 nm) via the University of Rochester HUCAPS system during a critical developmental window of CNS development, equivalent to human 3rd trimester, produced male-predominant neuropathological and behavioral characteristics common to multiple neurodevelopmental disorders, including autism spectrum disorder (ASD), in humans. The current study sought to determine whether vulnerability to fine (≤2.5 μm) and UFP air pollution exposure extends to embryonic periods of brain development in mice, equivalent to human 1st and 2nd trimesters. Pregnant mice were exposed 6 h/day from gestational days (GDs) 0.5-16.5 using the New York University VACES system to concentrated ambient fine/ultrafine particles at an average concentration of 92.69 μg/m3 over the course of the exposure period. At postnatal days (PNDs) 11-15, neuropathological consequences were characterized. Gestational air pollution exposures produced ventriculomegaly, increased corpus callosum (CC) area and reduced hippocampal area in both sexes. Both sexes demonstrated CC hypermyelination and increased microglial activation and reduced total CC microglia number. Analyses of iron deposition as a critical component of myelination revealed increased iron deposition in the CC of exposed female offspring, but not in males. These findings demonstrate that vulnerability of the brain to air pollution extends to gestation and produces features of several neurodevelopmental disorders in both sexes. Further, they highlight the importance of the commonalities of components of particulate matter exposures as a source of neurotoxicity and common CNS alterations.
authors.affiliation: Department of Environmental Medicine.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Klocke
authors.affiliation: Department of Environmental Medicine.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Allen
authors.affiliation: Department of Environmental Medicine.
authors.forename: Marissa
authors.initials: M
authors.lastname: Sobolewski
authors.affiliation: Department of Biomedical Genetics, University of Rochester School of Medicine, Rochester, New York 14642.
authors.forename: Margot
authors.initials: M
authors.lastname: Mayer-Pröschel
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Blum
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987.
authors.forename: Dana
authors.initials: D
authors.lastname: Lauterstein
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987.
authors.forename: Judith T
authors.initials: JT
authors.lastname: Zelikoff
authors.affiliation: Department of Environmental Medicine.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Cory-Slechta
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D005260:Female; D005865:Gestational Age; D008297:Male; D051379:Mice; D065886:Neurodevelopmental Disorders / Q000139:chemically induced* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000473:pathology
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter
keywords: air pollution; myelin.; neurotoxicology; white matter