Title: Particulate matter neurotoxicity in culture is size-dependent.
Authors: Gillespie, Patricia; Tajuba, Julianne; Lippmann, Morton; Chen, Lung-Chi; Veronesi, Bellina
Published In Neurotoxicology, (2013 May)
Abstract: Exposure to particulate matter (PM) air pollution produces inflammatory damage to the cardiopulmonary system. This toxicity appears to be inversely related to the size of the PM particles, with the ultrafine particle being more inflammatory than larger sizes. Exposure to PM has more recently been associated with neurotoxicity. This study examines if the size-dependent toxicity reported in cardiopulmonary systems also occurs in neural targets. For this study, PM ambient air was collected over a 2 week period from Sterling Forest State Park (Tuxedo, New York) and its particulates sized as Accumulation Mode, Fine (AMF) (>0.18-1μm) or Ultrafine (UF) (<0.18μm) samples. Rat dopaminergic neurons (N27) were exposed to suspensions of each PM fraction (0, 12.5, 25, 50μm/ml) and cell loss (as measured by Hoechst nuclear stain) measured after 24h exposure. Neuronal loss occurred in response to all tested concentrations of UF (>12.5μg/ml) but was only significant at the highest concentration of AMF (50μg/ml). To examine if PM size-dependent neurotoxicity was retained in the presence of other cell types, dissociated brain cultures of embryonic rat striatum were exposed to AMF (80μg/ml) or UF (8.0μg/ml). After 24h exposure, a significant increase of reactive nitrogen species (nitrite) and morphology suggestive of apoptosis occurred in both treatment groups. However, morphometric analysis of neuron specific enolase staining indicated that only the UF exposure produced significant neuronal loss, relative to controls. Together, these data suggest that the inverse relationship between size and toxicity reported in cardiopulmonary systems occurs in cultures of isolated dopaminergic neurons and in primary cultures of the rat striatum.
PubMed ID: 22057156
MeSH Terms: Air Pollution/adverse effects*; Analysis of Variance; Animals; Cells, Cultured; Corpus Striatum/cytology; Dose-Response Relationship, Drug; Embryo, Mammalian; Gutta-Percha/toxicity; Humans; Microglia/drug effects; Microglia/physiology; Microglia/ultrastructure; Neurons/drug effects; Particle Size*; Particulate Matter/toxicity*; Phosphopyruvate Hydratase/metabolism; Rats; Retrospective Studies; Spectrum Analysis