The brain is the central regulator for integration and control of responses to environmental cues. Previous studies suggest that air pollution may directly impact brain health by triggering the onset of chronic neuroinflammation. We hypothesize that nanoparticle components of combustion-generated air pollution may underlie these effects. To test this association, a microglial in vitro biological sensor model was used for testing neuroinflammatory response caused by low-dose nanoparticle exposure. The model was first validated using 20 nm silver nanoparticles (AgNP). Next, neuroinflammatory response was tested after exposure to size-selected 20 nm combustion-generated nanoparticles (CGNP) collected from a modern diesel engine. We show that low concentrations of CGNPs promote low-grade inflammatory response indicated by increased pro-inflammatory cytokine release (tumor necrosis factor-α), similar to that observed after AgNP exposure. We also demonstrate increased production of reactive oxygen species and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 phosphorylation in microglia after CGNP stimulation. Finally, we show conditioned media from CGNP-stimulated microglia significantly reduced hypothalamic neuronal survival in vitro. To our knowledge, this data show for the first time that exposure to AgNP and CGNP elicits microglial neuroinflammatory response through the activation of NF-κB.
Bibliographical noteFunding Information:
Acknowledgments: This work was funded by the US Department of Veterans Affairs BLR&D IK2 BX001686 (to T.A.B.), and grants from the University of Minnesota Healthy Foods, Healthy Lives Institute (to J.S., W.N., J.P.N. and T.A.B.) and the Minnesota Veterans Medical Research and Education Foundation (to T.A.B.). We thank Philippe Marambaud (Feinstein Institute for Medical Research, Manhasset, NY, USA) and Weihua Zhao (Methodist Hospital, Houston, TX, USA) for providing the BV2 cell line.
- Chronic inflammation
- Combustion-generated nanoparticles
- In vitro biosensor