The Constituent-Dependent Translocation Mechanism for PM_2.5 to Travel through the Olfactory Pathway

Abstract

The neurotoxic risk of PM2.5 is of worldwide concern, but the pathways through which PM2.5 gets to the central nervous system are still under debate. The olfactory pathway provides a promising shortcut to the brain, which bypasses the blood–brain barrier for PM2.5. However, direct evidence is lacking, and the translocation mechanism is still unclear. This study used the primary murine olfactory sensory neurons (OSNs) as an in vitro model to explore the translocation mechanism of PM2.5 in the olfactory system. We found that PM2.5 can be internalized into the OSNs via vesicle transportation. This process responds only to the water-insoluble compositions of PM2.5 (WIS-PM2.5) and cannot be affected by the water-soluble compositions of PM2.5 (WS-PM2.5). PM2.5 can further disrupt the integrity of the barrier constituted by the OSNs, and WS-PM2.5 plays a heightened role in inducing the damages. Our results suggested that both cellular and paracellular pathways are possibly involved in the translocation of PM2.5 in the olfactory system. More advanced microscopy techniques need to be developed to explore the whole translocation process in the olfactory–brain pathway in both in vitro and in vivo models.