165 - GLIA TREATED WITH PARTICULATE MATTER INCREASE NEURONAL INJURY THROUGH PAI-1 ACTIVATION
Abstract
Aims
Particulate matter 2.5 (PM2.5) can gain access to the lungs and the circulatory system and may sequentially cross the blood brain barrier (BBB). Recent data suggested that these particles reaching the brain may cause neurological disorders including AD and PD. However, the precise mechanisms by which PM2.5 contributed to neuronal damage have not been clarified. And, there is no study on how to prevent PM2.5-induced inflammation and neurotoxicity. In this study, we have demonstrated that PM2.5 increases the PAI-1 activity and neuroinflammation, and that natural compounds such as astaxanthin and Egb761 can prevent the subsequent neurotoxicity, mainly based on its anti-oxidative and anti-inflammatory properties.
Methods
In this regard, we examined 1) the mRNA expression of inflammatory mediators including iNOS, IL-1b, tPA, PAI-1, TNFa, c1q, TGFb and BDNF, 2) nitric oxide and reactive oxygen species production, 3) tPA and PAI-1 activity, and 4) neurite extension assay using the immunocytochemistry. We used a well-characterized Diesel particulate matter, PM2.5, from SIGMA-Aldrich.
Results
PM2.5 increased inflammatory cytokines such as IL-6 production in rat astrocytes, and PAI-1 mRNA expression activity in rat primary astrocytes. Astaxanthin and Egb761 attenuated PM2.5-induced increased ROS and other inflammatory cytokines expressions and prevented neuronal cell death in rat primary cortical neurons.
Conclusions
Our results show that PM2.5 activates the astrocytes through PAI-1 activation leading to neurotoxicity, and astaxanthin and Egb761 can prevent this through the inhibition of astrocytes activation. These results demonstrate that the potential beneficial effects of astaxanthin and Egb761 against air pollution exposure such as PM2.5.
