Combustion-derived air pollution is a multi-layered environmental toxin which is becoming a global health concern due to rapid urbanization. Air pollution contains mixtures of pro-inflammatory stimulants such as fine and ultra-fine particulate matter (PM&lt;2.5), gases (CO and NOx), and metals (Mn). Inhalation of these compound are linked to damage within the lungs and peripheral circulatory system which implicates damage to the central nervous system. In particular air pollutants can induce neurodegenerative pathology from neuroinflammation through the microglia. This specific study looks at the influence of systemic inflammation from air pollutants (diesel particulate matter; DPM) on the degeneration of neurons in an in vitro model. For this study, a trans-well plate (pore size 0.4 mm) with alveolar macrophages on the apical side and microglia on the basal side was utilized to model chronic inhalation of DPM (over 5-days). This allowed the transference of small proteins between the macrophages and the glia without the direct exposure to DPM to microglia. Activation of microglia was measured with HLA-DR and TLR-4 expression at day 1 to measure a one-time exposure compared to a day 5 chronic scenario to combustion-derived air pollutants. LPS (10ng/mL) was used as a positive control for TLR-4 pathway activation. After 5-days of chronic exposure the unhealthy microglia are co-cultured with healthy neurons to measure ROS generation, viability, and dopamine concentration. Microglial cells, through a feedback loop with surrounding neurons, release neurotoxic pro-inflammatory markers, these include, IL1β, IL6, TNF-α and CD86 and cause internal damage to neurons. Results indicated high expression of ROS measured through H2O2 and observed with confocal fluorescence microscopy. Viability was decreased after the introduction of unhealthy microglia and dopamine concentration also decreased subsequently compared to “healthy” co-culture model. This confirmed activated microglial cells release inflammatory markers which could implicate neurodegeneration and neuronal cellular damage from peripheral pathway exposures.

Neuroinflammation influences Neurodegeneration after chronic exposure to Combustion Products

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ACS Fall 2022

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