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 hippo campus, 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.

Development and testing of an online method to measure ambient fine particulate reactive oxygen species (ROS) based on the 2',7'-dichlorofluorescin (DCFH) assay

“…The amount of disruption depends on factors such as the amount of ROS introduced or produced within the system, the location of the introduction or production of the reactive species, the duration of the insult and a host of other factors, many of which have yet to be ascertained in nature as well as in scope (Barrett et al, 1999;Morgan et al, 2001;Oberdörster, 2004;Rothe and Valet, 1990;Squadrito et al, 2001;Sugamura and Keaney, 2011;Xia et al, 2006). Human exposure to ROS can occur by a number of known routes.…”

Atmospheric ultrafine particles promote vascular calcification via the NF-κB signaling pathway

“…The aqueous suspensions were pooled and were kept at Ϫ20°C to retain chemical stability. The PM suspension was reaerosolized by the protocol described by Morgan et al (33) and yielded highly concentrated PM for in vivo exposure in a controlled manner.…”

“…Particles were diffusion dried by passing through silica gel, and static charges were removed (Po-210 neutralizer) before entering exposure chambers. Mice were exposed to PM-aerosolized air (or control filtered air) via whole body animal exposure chambers as described previously (33). Briefly, five Ldlr Ϫ/Ϫ male mice (C57BL/6J background) at 12 wk of age in each group were placed on a high-fat diet (HFD D12492: 5.24 kcal/g, 34.9 g% fat, 26.2 g% protein, and 26.2 g% carbohydrate; Research Diets) and exposed to filtered air (FA) or UFP at a targeted concentration of ϳ400 g/m 3 for 5 h/day and 3 day/wk for 10 wk.…”

Xenobiotic pulmonary exposure and systemic cardiovascular response via neurological links

“…The associated disturbance of the glutamate-glutamine biosynthetic pathway may cause accumulation of glutamate in the extracellular compartments and lead to excitotoxicity (128). In vitro cultures of hippocampal slices exposed to nanoscale particulate urban air pollutants (Ͻ200 nm) showed an increased neurotoxicity by the glutamatergic agonist N-methyl-D-aspartic acid, whereas the glutamate receptor subunit (glutamate receptors of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subunit 1) was decreased significantly (90). Nasal instillation of titanium dioxide nanoparticles led to a 25-30% loss of neuronal pyramidal cells in the Cornu Ammonis area 1 region (CA1) and in the dentate gyrus associated with morphological and functional changes in the hippocampus (121).…”