Brominated Flame\nRetardant HBCD and Artificial Light\nat Night Synergically Caused Visual Disorder and Sleep Difficulty\nin Zebrafish Larvae

Sleep difficulty is a widespread health concern exacerbated\nby\nfactors such as light and chemical pollution. Artificial light at\nnight (ALAN) can disrupt natural sleep–wake cycles, whereas\nchemical pollutants can impair sleep-related processes. The prevalence\nof ALAN increases the health risk of coexposure, yet it has not gained\nsufficient attention. Meanwhile, visual inputs are important for sleep\nregulation, especially the non-image-forming circadian visual system\ncentered around melanopsin. This study evaluated the light perception\nability and sleep performance of zebrafish larvae exposed to flame\nretardant hexabromocyclododecanes (HBCDs) at environmentally relevant\nconcentrations (2.5 and 25 μg/L) and to cotreatment of HBCD\nand ALAN. HBCD induced a longer sleep latency of 34.59 min under 25\nμg/L (<i>p</i> < 0.01) versus control (26.04 min).\nThe situation was intensified by coexposure with low-level ALAN (10\nlx) to 48.04 min. Similar synergic effects were observed for upregulations\nof <i>Xenopus</i>-related melanopsin genes and downregulations\nof the melatonin synthesis gene <i>aanat2</i>, suggesting\na melanopsin–<i>aanat2</i>–sleep retina–brain\npathway. Image-forming opsins (<i>opn1sw1</i> and <i>opn1sw2</i>) were also activated by HBCD to 1.29–1.53-fold\n(<i>p</i> < 0.05), together with elevated retina glutamate,\nbut without synergic effects. Collectively, we found that HBCD and\nALAN coexposure caused synergic effects on the non-image-forming visual\nsystem and caused sleep difficulty in zebrafish larvae.