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Urban airborne PM_2.5-activated microglia mediate neurotoxicity through glutaminase-containing extracellular vesicles in olfactory bulb.

ABSTRACT: Emerging evidence has showed that exposure to airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM_2.5) is associated with neurodegeneration. Our previous studies in vitro found that PM_2.5 exposure causes primary neurons damage through activating microglia. However, the molecular mechanism of microglia-mediated neurotoxicity remains to elucidate. In this study, five groups (N = 13 or 10) of six-week-old male C57BL/6 mice were daily exposed to PM_2.5 (0.1 or 1 mg/kg/day body weight), Chelex-treated PM_2.5 (1 mg/kg/day body weight), PM_2.5 (1 mg/kg/day body weight) plus CB-839 (glutaminase inhibitor), or deionized water by intranasal instillation for 28 days, respectively. Compared with the control groups, We found that PM_2.5 triggered reactive oxygen species (ROS) generation and microglia activation evidenced by significant increase of ionized calcium binding adaptor molecule-1 (IBa-1) staining in the mouse olfactory bulbs (OB). Data from transmission electron microscope (TEM) images and Western blot analysis showed that PM_2.5 significantly increased extracellular vesicles (EVs) release from OB or murine microglial line BV2 cells, and glutaminase C (GAC) expression and glutamate generation in isolated OB and BV2 cells. However, treatment with N-acetylcysteine (NAC) or CB-839 significantly diminished the number of EVs and the expression of GAC and abolished PM_2.5-induced neurotoxicity. These findings provide new insights that PM_2.5 induces oxidative stress and microglia activation through its metal contents and glutaminase-containing EVs in OBs, which may serve as a potential pathway/mechanism of excessive glutamate generation in PM_2.5-induced neurotoxicity.

SUBMITTER: Chen X

PROVIDER: S-EPMC7364855 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionDespite the London Underground (LU) handling on average 2.8 million passenger journeys per day, the characteristics and potential health effects of the elevated concentrations of metal-rich PM2.5 found in this subway system are not well understood.MethodsSpatial monitoring campaigns were carried out to characterise the health-relevant chemical and physical properties of PM2.5 across the LU network, including diurnal and day-to-day variability and spatial distribution (above ground, depth below ground and subway line). Population-weighted station PM2.5 rankings were produced to understand the relative importance of concentrations at different stations and on different lines.ResultsThe PM2.5 mass in the LU (mean 88??g?m-3, median 28??g?m-3) was greater than at ambient background locations (mean 19??g?m-3, median 14??g?m-3) and roadside environments in central London (mean 22??g?m-3, median 14??g?m-3). Concentrations varied between lines and locations, with the deepest and shallowest submerged lines being the District (median 4??g?m-3) and Victoria (median 361??g?m-3 but up to 885??g?m-3). Broadly in agreement with other subway systems around the world, sampled LU PM2.5 comprised 47% iron oxide, 7% elemental carbon, 11% organic carbon, and 14% metallic and mineral oxides. Although a relationship between line depth and air quality inside the tube trains was evident, there were clear influences relating to the distance from cleaner outside air and the exchange with cabin air when the doors open. The passenger population-weighted exposure analysis demonstrated a method to identify stations that should be prioritised for remediation to improve air quality.ConclusionPM2.5 concentrations in the LU are many times higher than in other London transport Environments. Failure to include this environment in epidemiological studies of the relationship between PM2.5 and health in London is therefore likely to lead to a large exposure misclassification error. Given the significant contribution of underground PM2.5 to daily exposure, and the differences in composition compared to urban PM2.5, there is a clear need for well-designed studies to better understand the health effects of underground exposure.

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Urban airborne PM_2.5-activated microglia mediate neurotoxicity through glutaminase-containing extracellular vesicles in olfactory bulb.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Urban airborne PM2.5-activated microglia mediate neurotoxicity through glutaminase-containing extracellular vesicles in olfactory bulb.

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Urban airborne PM_2.5-activated microglia mediate neurotoxicity through glutaminase-containing extracellular vesicles in olfactory bulb.