Ambient NO2 exposure sex-specifically impairs myelin and contributes to anxiety and depression-like behaviors of C57BL/6J mice

NO2 is a common indoor and outdoor air pollutant, but its health effects are still controversial. Beside respiratory injury, more epidemiological studies show that inhalation of NO2 is associated with an increased risk of anxiety and depression. However, the causal relationship at the molecular level remains unclear. In the present study, we exposed adult C57BL/6J mice to NO2 (2.5 ppm, 5 h/day) for four weeks, and found anxiety and depression-like behaviors in male mice, but not female mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated that differentially expressed genes (DEGs) in the prefrontal cortex and cerebellum were closely associated with signal transduction pathways, such as axon guidance. Importantly, NO2 inhalation damaged the ultrastructure of myelin sheath and caused the abnormal expression of related genes in males, which partially contributed to mental disorders. We also found that prolactin (Prl), through its anti-inflammatory activity and remyelination, might play a major role in the sex-specific neurobehavioral disorder in male mice caused by NO2 exposure.

Automated summary

NO2 is a common indoor and outdoor air pollutant with potential health risks including anxiety and depression. Exposure to NO2 was found to induce anxiety and depression-like behaviors in male mice but not female mice in a study. Genomic analysis suggested that the effects of NO2 on nerve behavior disorders in male mice may be related to signal transduction pathways and myelin sheath ultrastructure. Prolactin may play a key role in the sex-specific neurobehavioral disorder in male mice caused by NO2 exposure.