Cell-based assays that predict in vivo neurotoxicity of urban ambient nano-sized particulate matter

Exposure to urban ambient particulate matter (PM) is associated with risk of Alzheimer's disease and accelerated cognitive decline in normal aging. Assessment of the neurotoxic effects caused by urban PM is complicated by variations of composition from source, location, and season. We compared...

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Bibliographic Details
Published in:Free radical biology & medicine 2019-12, Vol.145, p.33-41
Main Authors: Zhang, Hongqiao, Haghani, Amin, Mousavi, Amirhosein H., Cacciottolo, Mafalda, D'Agostino, Carla, Safi, Nikoo, Sowlat, Mohammad H., Sioutas, Constantinos, Morgan, Todd E., Finch, Caleb E., Forman, Henry Jay
Format: Article
Language:English
Subjects:
Air pollution
In vitro screening
Inflammation
Neurotoxicity
NF-κB
Particulate matter
Ultrafine particles
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Summary:Exposure to urban ambient particulate matter (PM) is associated with risk of Alzheimer's disease and accelerated cognitive decline in normal aging. Assessment of the neurotoxic effects caused by urban PM is complicated by variations of composition from source, location, and season. We compared several in vitro cell-based assays in relation to their in vivo neurotoxicity for NF-κB transcriptional activation, nitric oxide induction, and lipid peroxidation. These studies compared batches of nPM, a nanosized subfraction of PM2.5, extracted as an aqueous suspension, used in prior studies. In vitro activities were compared with in vivo responses of mice chronically exposed to the same batch of nPM. The potency of nPM varied widely between batches for NF-κB activation, analyzed with an NF-κB reporter in human monocytes. Three independently collected batches of nPM had corresponding differences to responses of mouse cerebral cortex to chronic nPM inhalation, for levels of induction of pro-inflammatory cytokines, microglial activation (Iba1), and soluble Aβ40 & −42 peptides. The in vitro responses of BV2 microglia for NO-production and lipid peroxidation also differed by nPM batch, but did not correlate with in vivo responses. These data confirm that batches of nPM can differ widely in toxicity. The in vitro NF-κB reporter assay offers a simple, high throughput screening method to predict the in vivo neurotoxic effects of nPM exposure. [Display omitted] •Cell-based assays for ambient nPM-induced NF-κB activation, lipid peroxidation and NO production were compared.•Batches of ambient nPM diverged in potency of cellular responses in vitro.•In vitro NF-κB reporter assay correlated best with ambient particle-mediated neurotoxicity in mice exposed to nPM.
ISSN:0891-5849
1873-4596
1873-4596
DOI:10.1016/j.freeradbiomed.2019.09.016