Neurotoxicity of Diesel Exhaust Particles.

Air pollution particulate matter (PM) is strongly associated with risks of accelerated cognitive decline, dementia and Alzheimer's disease. Ambient PM batches have variable neurotoxicity by collection site and season, which limits replicability of findings within and between research groups for analysis of mechanisms and interventions. Diesel exhaust particles (DEP) offer a replicable model that we define in further detail.Define dose- and time course neurotoxic responses of mice to DEP from the National Institute of Science and Technology (NIST) for neurotoxic responses shared by DEP and ambient PM.For dose-response, adult C57BL/6 male mice were exposed to 0, 25, 50, and 100μg/m3 of re-aerosolized DEP (NIST SRM 2975) for 5 h. Then, mice were exposed to 100μg/m3 DEP for 5, 100, and 200 h and assayed for amyloid-β peptides, inflammation, oxidative damage, and microglial activity and morphology.DEP exposure at 100μg/m3 for 5 h, but not lower doses, caused oxidative damage, complement and microglia activation in cerebral cortex and corpus callosum. Longer DEP exposure for 8 weeks/200 h caused further oxidative damage, increased soluble Aβ, white matter injury, and microglial soma enlargement that differed by cortical layer.Exposure to 100μg/m3 DEP NIST SRM 2975 caused robust neurotoxic responses that are shared with prior studies using DEP or ambient PM0.2. DEP provides a replicable model to study neurotoxic mechanisms of ambient PM and interventions relevant to cognitive decline and dementia.

Citation

Kristina Shkirkova, Krista Lamorie-Foote, Nathan Zhang, Andrew Li, Arnold Diaz, Qinghai Liu, Max A Thorwald, Jose A Godoy-Lugo, Brandon Ge, Carla D'Agostino, Zijiao Zhang, Wendy J Mack, Constantinos Sioutas, Caleb E Finch, William J Mack, Hongqiao Zhang. Neurotoxicity of Diesel Exhaust Particles. Journal of Alzheimer's disease : JAD. 2022 Aug 20

PMID: 36031897

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