0023-6152

AA00697606

7340476

Due to its extensive use and high stability in water–sediment systems, diazepam (DZP) has become an emerging pollutant of great concern. The adverse effects of DZP on fish have been well documented, but information on the molecular mechanisms underlying these toxic effects is still lacking. In this study, female Japanese medaka (Oryzias latipes) were exposed to DZP (800 ng/L) for 21 days, and responses in their behavior and brain transcriptomic profiles were investigated. With prolonged exposure, DZP significantly reduced the average swimming velocity (on day 21), frequency of active mobility (on day 14 and 21), and cumulative duration of active mobility (on day 14 and 21) in Japanese medaka, suggesting a typical sedative effect. The transcriptome analysis identified 913 differentially expressed genes (DEGs, 374 up–regulated and 539 down–regulated) in Japanese medaka exposed to DZP at 800 ng/L. The enrichment analysis revealed that the DEGs, which have molecular functions related to hormone activity and receptor functions, were significantly enriched in the pathways belonging to environmental information processing, genetic information processing, and cellular processes. Based on the protein-protein interaction (PPI) network, five DEGs were predicted as key driver genes, which may play critical roles in medicating the molecular networks of neuroactive ligand–receptor interaction (prl), histidine metabolism (suox), and estrogen signaling pathway (pgr, hsp90aa1.2, and foxa3).