Exposure to Ambient Fine Particulate Matter (PM2.5) Increases Vulnerability to Stress-Induced Depression in Mice, Potentially via the BDNF-CREB Signaling Pathway

Abstract

Epidemiological studies have found a strong association between ambient fine particulate matter (PM2.5) exposure and the occurrence and development of depression. However, their causal relationship and the underlying molecular mechanisms are unclear. In this study, male C57BL/6 mice underwent concentrated ambient PM2.5 (CAP) exposure for 3 months, followed by chronic stress treatment via single housing to assess their vulnerability to depression. Behavioral tests showed that PM2.5 exposure significantly induced depression-like behaviors in stressed but not unstressed mice. Magnetic resonance imaging (MRI) demonstrated both structural and functional alterations in the brain, especially in the nucleus accumbens (NAc), cerebral cortex (Cx), and olfactory bulb (OB). Furthermore, PM2.5 exposure triggered systemic inflammation, as evidenced by increased proinflammatory cytokine levels in circulation, and brain inflammation, as indicated by elevated IL-1β levels in the OB. Mechanistically, Western blot analysis revealed a significant decrease in levels of BDNF and CREB phosphorylation in the OB, indicating that dysregulation of the BDNF-CREB signaling pathway may be a potential molecular mechanism within the increased depression vulnerability in male mice caused by PM2.5 exposure. All of these results suggest that environmental factors such as PM2.5 may serve as a facilitating factor instead of a direct cause of depression, highlighting the importance of protecting stressed populations from high air pollution exposure and the necessity of corresponding effective intervention strategies.