title: Glutamatergic neurons in rodent models respond to nanoscale particulate urban air pollutants in vivo and in vitro.
abstract: BACKGROUND
  Inhalation of airborne particulate matter (PM) derived from urban traffic is associated with pathology in the arteries, heart, and lung; effects on brain are also indicated but are less documented.
  
  
  OBJECTIVE
  We evaluated rodent brain responses to urban nanoscale (< 200 nm) PM (nPM).
  
  
  METHODS
  Ambient nPM collected near an urban freeway was transferred to aqueous suspension and reaerosolized for 10-week inhalation exposure of mice or directly applied to rat brain cell cultures.
  
  
  RESULTS
  Free radicals were detected by electron paramagnetic resonance in the nPM 30 days after initial collection. Chronic inhalation of reaerosolized nPM altered selected neuronal and glial activities in mice. The neuronal glutamate receptor subunit (GluA1) was decreased in hippocampus, whereas glia were activated and inflammatory cytokines were induced [interleukin-1α (IL-1α), tumor necrosis factor-α (TNFα)] in cerebral cortex. Two in vitro models showed effects of nPM suspensions within 24-48 hr of exposure that involved glutamatergic functions. In hippocampal slice cultures, nPM increased the neurotoxicity of NMDA (N-methyl-d-aspartic acid), a glutamatergic agonist, which was in turn blocked by the NMDA antagonist AP5 [(2R)-amino-5-phosphonopentanoate]. In embryonic neuron cultures, nPM impaired neurite outgrowth, also blocked by AP5. Induction of IL-1α and TNFα in mixed glia cultures required higher nPM concentrations than did neuronal effects. Because conditioned media from nPM-exposed glia also impaired outgrowth of embryonic neurites, nPM can act indirectly, as well as directly, on neurons in vitro.
  
  
  CONCLUSIONS
  nPM can affect embryonic and adult neurons through glutamatergic mechanisms. The interactions of nPM with glutamatergic neuronal functions suggest that cerebral ischemia, which involves glutamatergic excitotoxicity, could be exacerbated by nPM.
authors: Davis School of Gerontology, University of Southern California, Los Angeles, California 90089, USA.
authors: Todd E
authors: TE
authors: Morgan
authors: David A
authors: DA
authors: Davis
authors: Nahoko
authors: N
authors: Iwata
authors: Jeremy A
authors: JA
authors: Tanner
authors: David
authors: D
authors: Snyder
authors: Zhi
authors: Z
authors: Ning
authors: Winnie
authors: W
authors: Kam
authors: Yu-Tien
authors: YT
authors: Hsu
authors: Jeremy W
authors: JW
authors: Winkler
authors: Jiu-Chiuan
authors: JC
authors: Chen
authors: Nicos A
authors: NA
authors: Petasis
authors: Michel
authors: M
authors: Baudry
authors: Constantinos
authors: C
authors: Sioutas
authors: Caleb E
authors: CE
authors: Finch
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000209:etiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects; D018698:Glutamic Acid / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000276:immunology; D066298:In Vitro Techniques; D019570:Inhalation Exposure / Q000032:analysis; D053582:Interleukin-1alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity; D009457:Neuroglia / Q000187:drug effects* / Q000276:immunology; D009474:Neurons / Q000187:drug effects*; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000819:agonists; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D015763:2-Amino-5-phosphonovalerate; D018698:Glutamic Acid; D053582:Interleukin-1alpha; D016202:N-Methylaspartate; D052638:Particulate Matter; D012333:RNA, Messenger; D018091:Receptors, AMPA; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions