Olfactory bulb microglia activation mediated neuronal death in real-ambient particulate matter exposure mice with depression-like behaviors

Growing evidence has indicated that air pollution is associated with depression, and damage of olfactory bulb (OB) is regarded as an early marker for depression. However, the toxicity of fine particulate matter (PM2.5) on OB and underlying mechanisms remains to be elucidated. In our study, a real-ambient PM2.5 exposure system was applied to explore the effects of PM2.5 on OB in C57BL/6 mice for 4 or 8 weeks. After 8 weeks exposure, the mice emerged potential depressive-like responses with reduction and disorder of cells in olfactory bulb tissues. Apoptosis and ultra-microstructure analysis indicated that the real-ambient PM2.5 exposure caused the neuronal death of OB. The immunofluorescence observation and KEGG pathway analysis revealed the real-ambient PM2.5 exposure induced microglia activation along with tumor necrosis factor α (TNFα)-mediated signaling enriched in OB of mice with depression-like behaviors. Moreover, results from ex vivo biosensor assay exhibited that PM2.5 might trigger systemic inflammation with increased levels of various proinflammatory factors to activate microglia. Further in vitro co-culture model identified that the PM2.5 evoked microglia cells activation with TNFα secretion and induced neuronal cells apoptosis via classical caspase3 signaling. Our findings provide new insights that PM2.5 induced microglia activation characterized by the release of TNFα to cause neurotoxicity either by direct action or by circulatory inflammation, resulting in OB damage, which may play a critical role in early diagnosis and pathogenic mechanisms for PM2.5 to cause depression. [Display omitted] •Real-ambient PM2.5 inhalation caused depressive-like responses with damage to olfactory bulb.•PM2.5 activated microglia to release TNFα to induce neuronal death.•TNFα-mediated caspase3 signaling takes part in neuronal apoptosis caused by PM2.5.•PM2.5 induced microglia activation either by particle translocation or by systemic inflammation.