Neurotoxicity of Diesel Exhaust Particles

Abstract

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Prenatal diesel exhaust exposure alters hippocampal synaptic plasticity in offspring

“…This finding is consistent with the observations made by Alvarez et al, who reported that PM2.5 exposure impairs cognitive development in children [ 29 ]. On the contrary, previous studies have shown that exposure to DEPs in adulthood can have molecular and/or behavioral effects on the nervous system [ 30 , 31 ]. The discrepancies observed among these different studies may be attributed to variations in exposure components, timing, and dosage.…”

Air pollution nanoparticle and alpha-synuclein fibrils synergistically decrease glutamate receptor A1, depending upon nPM batch activity

“…Another limitation is that nPM lacks the polycyclic aromatic hydrocarbons (PAHs) in total ambient air pollution [ 69 ]. Future studies of PD and air pollution could consider using model particles, such as diesel exhaust particles (DEP) from the National Institute of Science and Technology (SRM 2975), which contain PAHs and can reliably induce neurotoxic responses as those caused by active nPM batches [ 70 ].…”

Extracellular Vesicles for Alzheimer’s Disease and Dementia Diagnosis

“…While the primary focus of many studies has been on identifying biomarkers derived from EVs for differential diagnosis, there is a dire need to assess other metrics. These include prognostic insights, tracking disease progression, monitoring treatment responses, screening for risk, stratifying participants in clinical trials, interpreting drugs pharmacokinetics and pharmacodynamics and identifying responses to environmental toxins [232][233][234][235].…”