Exposure to inhaled particulate matter activates early markers of oxidative stress, inflammation and unfolded protein response in rat striatum

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.

Hydrogen Sulfide and/or Ammonia Reduces Spermatozoa Motility through AMPK/AKT Related Pathways

“…In the current study NH 4 Cl and/or Na 2 S increased TAK1. In line with previous studies where exposure to low levels of airborne irritants stimulated the markers of airway inflammation, where high level of H 2 S were detected in asthma patients, and exposure to different size fractions of PM activated inflammation and oxidative stress signals, Na 2 S and/or NH 4 Cl might elevate inflammatory factors to activate TAK1, which in turn enhances AMPK activation253132. Combinations of Na 2 S + NH 4 Cl significantly elevated the protein levels of AMPK and p-AMPK (Thr 172 ) in boar spermatozoa.…”

Ambient Air Pollution Exposures and Risk of Parkinson Disease

“…Chronic exposures to varying sizes and compositions of PM have been shown to induce pathological hallmarks of PD, including neuroinflammation, aggregation of α-synuclein, and neuronal oxidative stress (Block et al 2012; Calderón-Garcidueñas et al 2013), even in early childhood (Calderón-Garcidueñas et al 2013). Experimental data have also shown PD neuropathology in animals exposed to concentrated urban PM or diesel exhaust, including significant reduction of dopaminergic neurons in the substantia nigra (Veronesi et al 2005), elevated α-synuclein in the midbrain (Levesque et al 2011), and activation of unfolded protein response in the striatum (Guerra et al 2013). As a route of entry for air pollutants to the brain, evidence from animal studies suggests that the nasal cavity likely provides a direct transport pathway through which inhaled PM gains entry into the olfactory bulb and subsequently into the brain and brainstem (Block et al 2012; Calderón-Garcidueñas et al 2010, 2015).…”

“…For instance, one in vivo study suggested that the peripheral inflammatory response to PM 10 exposure in mice may trigger adverse effects in the brain (Farina et al 2013). Another murine study reported evidence of neuroinflammation, oxidative stress and unfolded protein responses in striatum activated by inhalation exposure to coarse PM (Guerra et al 2013). …”

Effects of Ambient Air Pollution Exposure on Olfaction: A Review

“…Diesel exhaust rich in nanoparticles (< 100 nm diameter) was also able to induce increased expression of N-methyl-D-aspartate (NMDA) receptor subunits and extracellular concentrations of glutamate, both of which may lead to excitotoxicity (Tin-Tin-Win-Shwe et al 2009). Exposure to PM of various sizes is also associated with elevated expression of the antioxidant heme oxygenase 1 (HO-1) in the olfactory bulb, as well as in other brain tissues (Guerra et al 2013). More generally, mice exposed to air in Mexico City, which is high in ambient air pollution, had elevated levels of IL-1β and CD14, which were associated with inflammatory responses, in their olfactory bulbs after 16 months of exposure, compared to controls breathing filtered air (Villarreal-Calderon et al 2010).…”