Title: Exposure to inhaled particulate matter activates early markers of oxidative stress, inflammation and unfolded protein response in rat striatum.
Authors: Guerra, R; Vera-Aguilar, E; Uribe-Ramirez, M; Gookin, G; Camacho, J; Osornio-Vargas, A R; Mugica-Alvarez, V; Angulo-Olais, R; Campbell, A; Froines, J; Kleinman, T M; De Vizcaya-Ruiz, A
Published In Toxicol Lett, (2013 Oct 24)
Abstract: To study central nervous system airborne PM related subchronic toxicity, SD male rats were exposed for eight weeks to either coarse (32 μg/m³), fine (178 μg/m³) or ultrafine (107 μg/m³) concentrated PM or filtered air. Different brain regions (olfactory bulb, frontal cortex, striatum and hippocampus), were harvested from the rats following exposure to airborne PM. Subsequently, prooxidant (HO-1 and SOD-2), and inflammatory markers (IL-1β and TNFα), apoptotic (caspase 3), and unfolded protein response (UPR) markers (XBP-1S and BiP), were also measured using real-time PCR. Activation of nuclear transcription factors Nrf-2 and NF-κB, associated with antioxidant and inflammation processes, respectively, were also analyzed by GSMA. Ultrafine PM increased HO-1 and SOD-2 mRNA levels in the striatum and hippocampus, in the presence of Nrf-2 activation. Also, ultrafine PM activated NF-κB and increased IL-1β and TNFα in the striatum. Activation of UPR was observed after exposure to coarse PM through the increment of XBP-1S and BiP in the striatum, accompanied by an increase in antioxidant response markers HO-1 and SOD-2. Our results indicate that exposure to different size fractions of PM may induce physiological changes (in a neuroanatomical manner) in the central nervous system (CNS), specifically within the striatum, where inflammation, oxidative stress and UPR signals were effectively activated.
PubMed ID: 23892126
MeSH Terms: Air Pollutants/chemistry; Air Pollutants/toxicity*; Animals; Biomarkers/metabolism; Central Nervous System Agents/chemistry; Central Nervous System Agents/toxicity*; Corpus Striatum/drug effects*; Corpus Striatum/immunology; DNA-Binding Proteins/biosynthesis; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Heat-Shock Proteins/biosynthesis; Heat-Shock Proteins/genetics; Heat-Shock Proteins/metabolism; Heme Oxygenase (Decyclizing)/biosynthesis; Heme Oxygenase (Decyclizing)/genetics; Heme Oxygenase (Decyclizing)/metabolism; Male; Mexico; Nerve Tissue Proteins/biosynthesis; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neurons/drug effects*; Neurons/immunology; Oxidative Stress/drug effects*; Particle Size; Particulate Matter/chemistry; Particulate Matter/toxicity*; Rats; Rats, Sprague-Dawley; Regulatory Factor X Transcription Factors; Superoxide Dismutase/biosynthesis; Superoxide Dismutase/genetics; Superoxide Dismutase/metabolism; Transcription Factors/biosynthesis; Transcription Factors/genetics; Transcription Factors/metabolism; Unfolded Protein Response/drug effects*; Up-Regulation/drug effects; X-Box Binding Protein 1