Fishery Resource and Environment Research Center , Chinese Academy of Fishery Sciences , Beijing 100141 , People's Republic of China.
College of Sciences , China Agricultural University , Beijing 100193 , People's Republic of China.
Environ Sci Technol. 2019 Dec 17;53(24):14638-14648. doi: 10.1021/acs.est.9b04097. Epub 2019 Nov 25.
In this study, the influence of bisphenol F (BPF) toward central nervous system (CNS) was assessed using zebrafish embryos. We found that BPF could induce significant neurotoxicity toward zebrafish embryos, including inhibited locomotion, reduced moving distance, and CNS cell apoptosis at an effective concentration of 0.0005 mg/L. Immunofluorescence assay showed that both microglia and astrocyte in zebrafish brain were significantly activated by BPF, indicating the existence of neuroinflammatory response. Peripheral motor neuron development was significantly inhibited by BPF at 72 hpf. RNA-seq data indicated that neuronal developmental processes and cell apoptosis pathways were significantly affected by BPF exposure, which was consistent with the phenotypic results. Chip-seq assay implied that the transcriptional changes were not mediated by ERα. Additionally, no significant change was found in neurotransmitter levels (5-hydroxytryptamine, dopamine, and acetylcholine) or acetylcholinesterase (Ache) enzyme activity after BPF exposure, indicating that BPF may not affect neurotransmission. In conclusion, BPF could lead to abnormal neural outcomes during zebrafish early life stage through inducing neuroinflammation and CNS cell apoptosis even at environmentally relevant concentration.
在这项研究中，使用斑马鱼胚胎评估了双酚 F（BPF）对中枢神经系统（CNS）的影响。我们发现，BPF 可在有效浓度 0.0005mg/L 下诱导斑马鱼胚胎产生显著的神经毒性，包括运动抑制、移动距离减少和 CNS 细胞凋亡。免疫荧光分析表明，BPF 可显著激活斑马鱼脑中的小胶质细胞和星形胶质细胞，表明存在神经炎症反应。BPF 在 72 hpf 时可显著抑制周围运动神经元的发育。RNA-seq 数据表明，神经元发育过程和细胞凋亡途径受到 BPF 暴露的显著影响，这与表型结果一致。芯片-seq 分析表明，转录变化不是由 ERα 介导的。此外，BPF 暴露后神经递质水平（5-羟色胺、多巴胺和乙酰胆碱）或乙酰胆碱酯酶（Ache）酶活性没有明显变化，表明 BPF 可能不会影响神经传递。总之，BPF 即使在环境相关浓度下也可通过诱导神经炎症和中枢神经系统细胞凋亡导致斑马鱼早期生命阶段出现异常神经结局。
