Excessive selenium affects neural development and locomotor behavior of zebrafish embryos

Selenium is an essential micronutrient derived from daily diet to maintain the normal growth and development of vertebrates. Excessive selenium intake will induce cardiovascular toxicity, reproductive toxicity and neurotoxicity. However, there have been few studies of the toxic effects of selenium on neural development and locomotor behavior. In this study, newly fertilized zebrafish embryos were treated with selenium. As a result, selenium treatment at the concentration of 0.5 µM decreased the moving speed and distance and blunted the touch response of zebrafish embryos. TUNEL assay and immunofluorescence analysis revealed that selenium induced nervous system impairment including promoted cell apoptosis, proliferation and neuroinflammation, and decreased neurons in zebrafish embryos. RNA-seq and RT-PCR results indicated that selenium treatment significantly decreased the expression of the dopaminergic neuron, motor neuron, GABAergic neuron and neurotransmitter transport marker genes in zebrafish embryos. The expression of PPAR signaling pathway marker genes was significantly down-regulated in selenium-treated embryos. Two PPAR agonists (rosiglitazone and bezafibrate) and an anti-cancer drug (cisplatin) were tested for their effects to alleviate selenium-induced locomotor defects. Rosiglitazone and bezafibrate could restore the expression of some neural marker genes but could not fully rescue the selenium-induced locomotor behavior defects. The supplementation of cisplatin could restore the dysfunctional locomotor behavior and the abnormal expression of the PPAR and neural marker genes to almost the normal levels. In conclusion, the results of this study reveal that selenium-induced neural development and locomotor behavior defects are caused by multiple complex factors including PPAR signaling, and all the factors might be recovered by cisplatin through unknown mechanisms. •Excess selenium affects neural development and locomotor behavior of zebrafish.•PPAR signaling is involved in the formation of selenium-induced locomotor defects.•Cisplatin recovers locomotor defects via multiple factors including PPAR signaling.