title: Early postnatal exposure to ultrafine particulate matter air pollution: persistent ventriculomegaly, neurochemical disruption, and glial activation preferentially in male mice.
abstract: BACKGROUND
  Air pollution has been associated with adverse neurological and behavioral health effects in children and adults. Recent studies link air pollutant exposure to adverse neurodevelopmental outcomes, including increased risk for autism, cognitive decline, ischemic stroke, schizophrenia, and depression.
  
  
  OBJECTIVE
  We sought to investigate the mechanism(s) by which exposure to ultrafine concentrated ambient particles (CAPs) adversely influences central nervous system (CNS) development.
  
  
  METHODS
  We exposed C57BL6/J mice to ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient Particle System or to filtered air on postnatal days (PNDs) 4-7 and 10-13, and the animals were euthanized either 24 hr or 40 days after cessation of exposure. Another group of males was exposed at PND270, and lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified.
  
  
  RESULTS
  We observed ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice exposed to CAPs, and it persisted through young adulthood. In addition, CAPs-exposed males generally showed decreases in developmentally important CNS cytokines, whereas in CAPs-exposed females, we observed a neuroinflammatory response as indicated by increases in CNS cytokines. We also saw changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increased hippocampal glutamate in CAPs-exposed males.
  
  
  CONCLUSIONS
  We observed brain region- and sex-dependent alterations in cytokines and neurotransmitters in both male and female CAPs-exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed only in CAPs-exposed male mice. Ventriculomegaly is a neuropathology that has been associated with poor neurodevelopmental outcome, autism, and schizophrenia. Our findings suggest alteration of developmentally important neurochemicals and lateral ventricle dilation may be mechanistically related to observations linking ambient air pollutant exposure and adverse neurological/neurodevelopmental outcomes in humans.
authors.affiliation: Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Allen
authors.forename: Xiufang
authors.initials: X
authors.lastname: Liu
authors.forename: Sean
authors.initials: S
authors.lastname: Pelkowski
authors.forename: Brian
authors.initials: B
authors.lastname: Palmer
authors.forename: Katherine
authors.initials: K
authors.lastname: Conrad
authors.forename: Günter
authors.initials: G
authors.lastname: Oberdörster
authors.forename: Douglas
authors.initials: D
authors.lastname: Weston
authors.forename: Margot
authors.initials: M
authors.lastname: Mayer-Pröschel
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Cory-Slechta
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution / Q000706:statistics & numerical data; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006849:Hydrocephalus / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia; D018377:Neurotransmitter Agents / Q000378:metabolism; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D012737:Sex Factors
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D018377:Neurotransmitter Agents; D052638:Particulate Matter