Particulate matter neurotoxicity in culture is size-dependent

Gillespie, Patricia A.; Tajuba, Julianne; Lippmann, Morton; Chen, Lung Chi; Veronesi, Bellina

doi:10.1016/j.neuro.2011.10.006

Cited by 59 publications

(46 citation statements)

References 66 publications

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“…However, a few studies evaluated the impact of size [29], [30] and charge [30], [31] of PM on bioreactivity in in vitro cell model systems. In addition, the source (coal, DEP, oil) and handling of PM were shown to alter the bioreactivity in a rat alveolar epithelial cell line (RLE-6TN) [32].…”

Section: Resultsmentioning

confidence: 99%

Variability in Bioreactivity Linked to Changes in Size and Zeta Potential of Diesel Exhaust Particles in Human Immune Cells

et al. 2014

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Acting as fuel combustion catalysts to increase fuel economy, cerium dioxide (ceria, CeO2) nanoparticles have been used in Europe as diesel fuel additives (Envirox™). We attempted to examine the effects of particles emitted from a diesel engine burning either diesel (diesel exhaust particles, DEP) or diesel doped with various concentrations of CeO2 (DEP-Env) on innate immune responses in THP-1 and primary human peripheral blood mononuclear cells (PBMC). Batches of DEP and DEP-Env were obtained on three separate occasions using identical collection and extraction protocols with the aim of determining the reproducibility of particles generated at different times. However, we observed significant differences in size and surface charge (zeta potential) of the DEP and DEP-Env across the three batches. We also observed that exposure of THP-1 cells and PBMC to identical concentrations of DEP and DEP-Env from the three batches resulted in statistically significant differences in bioreactivity as determined by IL-1β, TNF-α, IL-6, IFN-γ, and IL-12p40 mRNA (by qRT-PCR) and protein expression (by ELISPOT assays). Importantly, bioreactivity was noted in very tight ranges of DEP size (60 to 120 nm) and zeta potential (−37 to −41 mV). Thus, these physical properties of DEP and DEP-Env were found to be the primary determinants of the bioreactivity measured in this study. Our findings also point to the potential risk of over- or under- estimation of expected bioreactivity effects (and by inference of public health risks) from bulk DEP use without taking into account potential batch-to-batch variations in physical (and possibly chemical) properties.

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Section: Resultsmentioning

confidence: 99%

Variability in Bioreactivity Linked to Changes in Size and Zeta Potential of Diesel Exhaust Particles in Human Immune Cells

et al. 2014

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“…The present study addresses interactions of age and TRAP by chronically exposing young (3 month) and older (18 month) female B6 mice to nPM, a nano-size subfraction of ambient PM 2.5 , which has greater cytotoxicity in vivo and in vitro than larger PM ( Gillespie et al, 2013, Li et al, 2003). In neonatal neuron cultures nPM inhibited neurite outgrowth via TNFa and TNFR1, caused growth cone collapse (Cheng et al, 2016a).…”

Section: Introductionmentioning

confidence: 99%

Traffic-related air pollution impact on mouse brain accelerates myelin and neuritic aging changes with specificity for CA1 neurons

Woodward

Pakbin

Saffari

et al. 2017

Neurobiology of Aging

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Traffic-related air pollution (TRAP) is associated with lower cognition and reduced white matter volume in older adults, specifically for particulate matter <2.5 μm diameter (PM2.5). Rodents exposed to TRAP have shown microglial activation and neuronal atrophy. We further investigated age differences of TRAP exposure, with focus on hippocampus for neuritic atrophy, white matter degeneration, and microglial activation. Young and middle-aged mice (3 and 18 month female C57BL/6J) were exposed to nanoscale-PM (nPM, <0.2 μm diameter). Young mice showed selective changes in the hippocampal CA1 region, with neurite atrophy (−25%), decreased MBP (−50%), and increased Iba1 (+50%), with dentate gyrus relatively unaffected. Exposure to nPM of young mice decreased GluA1 protein (−40%) and increased TNFa mRNA (10×). Older controls had age changes approximating nPM effects on young, with no response to nPM, suggesting an age ceiling effect. The CA1 selective vulnerability in young mice parallels CA1 vulnerability in Alzheimer’s disease. We propose that TRAP associated human cognitive and white matter changes involve hippocampal responses to nPM that begin at younger ages.

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“…The same seems to be true with regard to the CNS, as markers of oxidative stress and neuroinflammation are increased as a result of exposure to air pollution (Block and Calderon-Garcidienas, 2009; Genc et al, 2012). Some in vitro studies have shown that PM is cytotoxic, and that toxicity is size-dependent, with UFPM being able to better enter the cells and exert toxic effects (Block et al, 2004; Kreyling et al, 2004; Win-Shwe and Fujimaki, 2011; Gillespie et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

“…A few in vitro studies have examined the effects of DE particles (DEP) on the CNS, particularly on dopaminergic neurons (Block et al, 2004; Gillespie et al, 2012; Levesque et al, 2011b). An earlier study by Block et al (2004) is of great interest, as it showed that DEP could activate microglia, and that microglia-derived oxidant species caused the demise of dopaminergic neurons (Block et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Microglia mediate diesel exhaust particle-induced cerebellar neuronal toxicity through neuroinflammatory mechanisms

2016

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In addition to the well-established effects of air pollution on the cardiovascular and respiratory systems, emerging evidence has implicated it in inducing negative effects on the central nervous system. Diesel exhaust particulate matter (DEP), a major component of air pollution, is a complex mixture of numerous toxicants. Limited studies have shown that DEP-induced dopaminergic neuron dysfunction is mediated by microglia, the resident immune cells of the brain. Here we show that mouse microglia similarly mediate primary cerebellar granule neuron (CGN) death in vitro. While DEP (0, 25, 50, 100 µg/2 cm2) had no effect on CGN viability after 24 h of treatment, in the presence of primary cortical microglia neuronal cell death increased by 2–3-fold after co-treatment with DEP, suggesting that microglia are important contributors to DEP-induced CGN neurotoxicity. DEP (50 µg/2 cm2) treatment of primary microglia for 24 h resulted in morphological changes indicative of microglia activation, suggesting that DEP may induce the release of cytotoxic factors. Microglia-conditioned medium after 24 h treatment with DEP, was also toxic to CGNs. DEP caused a significant increase in reactive oxygen species in microglia, however, antioxidants failed to protect neurons from DEP/microglia-induced toxicity. DEP increased mRNA levels of the pro-inflammatory cytokines IL-6 and IL1-β, and the release of IL-6. The antibiotic minocycline (50 µM) and the peroxisome proliferator-activated receptor-γ agonist pioglitazone (50 µM) attenuated DEP-induced CGN death in the co-culture system. Microglia and CGNs from male mice appeared to be somewhat more susceptible to DEP neurotoxicity than cells from female mice possibly because of lower paraoxonase-2 expression. Together, these results suggest that microglia-induced neuroinflammation may play a critical role in modulating the effect of DEP on neuronal viability.

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Particulate matter neurotoxicity in culture is size-dependent

Cited by 59 publications

References 66 publications

Variability in Bioreactivity Linked to Changes in Size and Zeta Potential of Diesel Exhaust Particles in Human Immune Cells

Variability in Bioreactivity Linked to Changes in Size and Zeta Potential of Diesel Exhaust Particles in Human Immune Cells

Traffic-related air pollution impact on mouse brain accelerates myelin and neuritic aging changes with specificity for CA1 neurons

Microglia mediate diesel exhaust particle-induced cerebellar neuronal toxicity through neuroinflammatory mechanisms

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