Brominated Flame Retardant HBCD and Artificial Light at Night Synergically Caused Visual Disorder and Sleep Difficulty in Zebrafish Larvae.

Sleep difficulty is a widespread health concern exacerbated by factors such as light and chemical pollution. Artificial light at night (ALAN) can disrupt natural sleep-wake cycles, whereas chemical pollutants can impair sleep-related processes. The prevalence of ALAN increases the health risk of coexposure, yet it has not gained sufficient attention. Meanwhile, visual inputs are important for sleep regulation, especially the non-image-forming circadian visual system centered around melanopsin. This study evaluated the light perception ability and sleep performance of zebrafish larvae exposed to flame retardant hexabromocyclododecanes (HBCDs) at environmentally relevant concentrations (2.5 and 25 μg/L) and to cotreatment of HBCD and ALAN. HBCD induced a longer sleep latency of 34.59 min under 25 μg/L ( p < 0.01) versus control (26.04 min). The situation was intensified by coexposure with low-level ALAN (10 lx) to 48.04 min. Similar synergic effects were observed for upregulations of Xenopus -related melanopsin genes and downregulations of the melatonin synthesis gene aanat2 , suggesting a melanopsin- aanat2 -sleep retina-brain pathway. Image-forming opsins ( opn1sw1 and opn1sw2 ) were also activated by HBCD to 1.29-1.53-fold ( p < 0.05), together with elevated retina glutamate, but without synergic effects. Collectively, we found that HBCD and ALAN coexposure caused synergic effects on the non-image-forming visual system and caused sleep difficulty in zebrafish larvae.