A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae.

摘要: Abstract Tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP), an extensively used organophosphorus flame retardant, is frequently detected in various environmental media and biota, has been demonstrated as neurotoxic. Autophagy proposed a protective mechanism against toxicant-induced neurotoxicity. The purpose of the present study was to investigate effect TDCIPP exposure on autophagy, its role TDCIPP-induced developmental Zebrafish embryos (2–120 h post-fertilization [hpf]) were exposed (0, 5, 50 500 μg/l) model neurotoxic chemical, chlorpyrifos (CPF, 100 μg/l). endpoints, locomotive behavior, cholinesterase activities, gene protein expression related neurodevelopment autophagy measured larvae. Our results demonstrate that (500 μg/l) CPF causes toxicity, including reduced hatching survival rates increased malformation rate (e.g., spinal curvature), well altered locomotor behavior. selected neurodevelopmental markers mbp, syn2a, α1-tubulin) significantly down-regulated zebrafish Treatment with inhibits AChE BChE, while (0–500 μg/l) exerts no effects these enzymes. Furthermore, conversion microtubule-associated I (LC3 I) LC3 II In addition, also activates transcription several critical genes (e.g. Becn1, atg3, atg5, map1lc3b sqstm1). To further induced neurotoxicity, inducer (rapamycin, Rapa, 1 nM) inhibitor (chloroquine, CQ, 1 μM) used. rate, mbp а1-tubulin proteins all larvae treated Rapa compared alone. contrast, co-treatment CQ exacerbated toxicity. Taken together, our confirm induces which plays neurotoxicity