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

作者: Hongqiao Zhang , Amin Haghani , Amirhosein H. Mousavi , Mafalda Cacciottolo , Carla D'Agostino

DOI: 10.1016/J.FREERADBIOMED.2019.09.016

关键词: NeurotoxicityNitric oxideLipid peroxidationPharmacologyIn vitroChemistryToxicityIn vivoReporter geneCognitive decline

摘要: Exposure to urban ambient particulate matter (PM) is associated with risk of Alzheimer's disease and accelerated cognitive decline in normal aging. Assessment the neurotoxic effects caused by PM complicated variations composition from source, location, season. We compared several vitro cell-based assays relation their vivo neurotoxicity for NF-κB transcriptional activation, nitric oxide induction, lipid peroxidation. These studies batches nPM, a nanosized subfraction PM2.5, extracted as an aqueous suspension, used prior studies. In activities were responses mice chronically exposed same batch nPM. The potency nPM varied widely between analyzed reporter human monocytes. Three independently collected had corresponding differences mouse cerebral cortex chronic inhalation, levels induction pro-inflammatory cytokines, microglial activation (Iba1), soluble Aβ40 & -42 peptides. BV2 microglia NO-production peroxidation also differed batch, but did not correlate responses. data confirm that can differ toxicity. assay offers simple, high throughput screening method predict exposure.

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