双酚G对斑马鱼神经行为的影响及机制研究

Effects and mechanisms of Bisphenol G on the neurobehavior of zebrafish

使用双酚G(BPG)慢性染毒成年斑马鱼,以评估其毒性效应和作用机制.结果表明,50μg/L BPG染毒组显著降低了斑马鱼的移动距离和上下水层切换频率,在底部累积时间增加了22.7%,表现出显著的行为异常;5和50μg/L染毒导致社交距离分别增加了126.8%和151.2%,社交累积时间分别减少了80.1%和73.7%,表现出显著的社交障碍.切片染色显示脑结构和肠道绒毛受损以及肠道杯状细胞数量和粘液分泌增加,表明潜在的肠道炎症以及神经疾病的发生.进一步的靶向代谢组学显示肠脑神经递质水平紊乱,色氨酸、GABA、谷氨酰胺、去甲肾上腺素、胆碱和组胺等水平显著改变;KEGG通路富集分析表明,苯丙氨酸、酪氨酸和色氨酸生物合成,缬氨酸、亮氨酸和异亮氨酸生物合成,精氨酸生物合成及苯丙氨酸代谢是主要受影响通路且存在性别差异,这些通路通过干扰神经递质转运和稳态,调控斑马鱼行为.BPG染毒,斑马鱼表现出显著的神经行为毒性效应和肠脑神经递质代谢紊乱,肠脑调节可能参与介导该效应.

This work evaluated the chronic toxic target and mechanism of bisphenol G(BPG)toward adult zebrafish through chronic exposure.The results showed that BPG exposure resulted in abnormal behavior of zebrafish.In the 50μg/L BPG exposure group,the zebrafish moving distance and switching frequency between the upper and lower zones were significantly reduced,and the accumulative time at the bottom was increased by 22.7%.Both 5and 50μg/L exposures significantly changed the social behavior of zebrafish,with increased social distance by(126.8%and 151.2%of control,respectively),reduced contact time(80.1%and 73.7%of control,respectively),and showed significant anxiety-like behavior and cognitive impairment.Section staining showed injured brain structure and intestinal villi,as well as increased intestinal goblet cell and mucus secretion,indicating potential intestinal inflammation and the development of neurological diseases.Further targeted metabolomics revealed disordered levels of neurotransmitters in the gut and brain,with significant changes in levels of tryptophan,GABA,glutamine,norepinephrine,choline,and histamine.Enrichment analysis of the KEGG pathway showed that phenylalanine,tyrosine and tryptophan biosynthesis;valine,leucine and isoleucine biosynthesis;arginine biosynthesis and phenylalanine metabolism were mainly affected pathways and with gender discriminations.These pathways regulate zebrafish behavior by interfering with the transport and homeostasis of neurotransmitters.In conclusion,BPG induced significant neurobehavioral toxicity and neurotransmitter disorder in the brain and intestine of zebrafish,and the gut-brain axis may be involved in mediating this effect.