Transcriptome profiling reveals toxicity mechanisms following sertraline exposure in the brain of juvenile zebrafish (Danio rerio)

Sertraline (SER) is one of the most commonly detected antidepressants in the aquatic environment that can negatively affect aquatic organisms at low concentrations. Despite some knowledge on its acute toxicity to fish, the effects of chronic SER exposure remain poorly understood along with any underlying mechanisms of SER-induced toxicity. To address this knowledge gap, the effects of chronic exposure to three SER concentrations from low to high were investigated in zebrafish. Juvenile zebrafish were exposed to three concentrations of 1, 10, or 100 μg/L of SER for 28 d, after which indicators of oxidative stress and neurotoxicity in the brain were measured. Superoxide dismutase (SOD) activity was significantly enhanced by SER at 1 up to 100 μg/L, and catalase (CAT) activity was significantly induced by SER at 1 or 10 μg/L. The activity of acetylcholinesterase (AChE) was significantly induced by 10 and 100 μg/L of SER, and the serotonin (5-HT) level was significantly increased by all three concentrations of SER. To ascertain mechanisms of SER-induced toxicity, transcriptomics was conducted in the brain of zebrafish following 100 μg/L SER exposure. The molecular signaling pathways connected with circadian system and the immune system were significantly altered in the zebrafish brain. Based on transcriptomic data, the expression levels of six circadian clock genes were measured, and three genes were significantly altered in relative abundance in fish from all experimental treatments with SER, including cryptochrome circadian regulator 2 (cry2), period circadian clock 2 (per2), and period circadian clock 3 (per3). We hypothesize that the circadian system may be related to SER-induced neurotoxicity and oxidative stress in the central nervous system. This study reveals potential mechanisms and key events (i.e., oxidative stress and neurotoxicity) associated with SER-induced toxicity, and improves understanding of the molecular and biochemical pathways putatively perturbed by SER.