Coal dust particles induce anxiety-like behaviors in the mice through lung-brain crosstalk

Respirable coal dust particles (CDP), a major occupational inhalation hazard generated during coal mining and processing, can deposit deeply in the lung and induce persistent oxidative stress, inflammation, and tissue injury. However, the potential effects of CDP inhalation exposure on nervous system and mental health in the crosstalk between the lung and the brain remain elusive. In this research, C57BL/6 J mice were exposed to CDP of 25 mg/Kg body weight every week for 12 weeks. We found that long-term CDP significantly induced anxiety-like behaviors in mice, accompanied with histopathology changes, manifested neuronal shrinkage and Nissl body disintegration, and markedly elevated CORT (1.93-fold) in serum, and reduced 5-HT (79.36%), BDNF (80.75%), GABA (65.15%), and DA (82.88%) in cortex relative to controls. Transcriptomic studies in cortex tissue have demonstrated key pathways and factors of mental disorder. Subsequently, we observed abnormal morphology of lung structure, as well as impaired physiological barrier upon CDP treatment. Meanwhile, CDP exposure may induce lung microbial dysbiosis, with Gram-negative bacteria becoming the dominant species, contributing to the production of lipopolysaccharide (LPS). Mechanistically, chronic CDP exposure promoted pulmonary and systemic inflammation, accompanied by increased circulating LPS level and activation of TLR4/MyD88/NF-κB signaling pathway, ultimately contributing to anxiety-like behaviors.