胚胎期及哺乳期全氟辛烷磺酸盐(PFOS)暴露对大鼠长时程突触可塑性影响的miRNA组学研究

为探讨PFOS胚胎期及哺乳期暴露对动物子代学习记忆能力影响的分子机理,采用微小RNA(miRNA)芯片技术检测PFOS胚胎期及哺乳期暴露对出生第1和7天大鼠脑组织miRNA表达的影响,分析突触可塑性相关miRNA表达的差异变化。结果显示,经PFOS暴露后出生第1和7天的大鼠脑组织中分别有24和17个miRNA发生显著性差异表达(p<0.05),其中与突触传递和神经递质转运等相关的miRNA的差异表达最为显著,主要包括miR-466b、miR-672、miR-297、miR-674-3p和miR-207。差异表达miRNA的路径分析显示出生后1和7d的大鼠的长时程增强效应(LTP)均受PFOS显著影响(p<0.05),这说明PFOS胚胎期及哺乳期暴露可能通过影响LTP的形成、发展和维持过程对大鼠子代大脑学习记忆能力造成威胁,并且miR-466b、miR-672、miR-297、miR-674-3p和miR-207可能参与了其中的调控过程。

Exploration of the Potential Effect of Perfluorooctane Sulfonate (PFOS) Neonatal Exposure on Long-term Potentiation during Synaptic Transimission by MiRNA Microarray

To explore the molecular mechanism underlying the toxic effect of PFOS prenatal and neonatal exposure on the study and memory ability of offspring, miRNA arrays were used to profile the expression of brain miRNAs in neonatal rats on postnatal day (PND) 1 and 7 with prenatal and neonatal exposure of PFOS. The results showed that twenty-four brain miRNAs on PND 1 and seventeen on PND 7 rats were significantly changed after PFOS exposure (p< 0.05). miR-466b, miR-672, miR-297, miR-674-3p and miR-207, which participate in neurotransmitter transport and synaptic transmission, showed the highest differential expression. The analysis of pathways associated with differentially expressed miRNAs indicated that long-term potentiation (LTP) in rat pups on PND 1 and 7 rats were significantly affected by PFOS exposure (p<0.05). It is demonstrated that prenatal and neonatal exposure of PFOS could threaten the study and memory ability of rat offspring through the effect of the formation, maturation and maintenance of LTP. Moreover, miR-466b, miR-672, miR-297, miR-674-3p and miR-207 might be involved in the above process.