Fang Fang, Song Ruixue, Ling Xiaomin, Peng Mengyuan, Xue Zhanggang, Cang Jing
Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
Life Sci. 2017 Apr 15;175:16-22. doi: 10.1016/j.lfs.2017.03.003. Epub 2017 Mar 7.
Sevoflurane is widely used in non-obstetric surgeries of pregnant women, but its influences on fetal brain are still not fully known. We set out to assess the effects of multiple maternal sevoflurane exposure on neurogenesis and cognitive dysfunction in fetus and offspring. Pregnant mice (gestational day 15.5) and cultured mouse neural stem cells (NSCs) received daily sevoflurane exposure (2.5%×2h and 4.1%×2h respectively) for three consecutive days. Cognitive function of the offspring was determined with the Morris water maze. The expression of Ccnd1 and Pax6 in fetal brains and NSCs were analyzed by immunofluorescence, Western blot and qPCR. The neurogenesis was evaluated by BrdU staining. Results showed that multiple sevoflurane exposure in pregnant mice caused the decrease of Pax6 and Ccnd1 expression, the inhibition of NSCs proliferation and fetal hippocampus neurogenesis, which may contribute to the impaired learning and memory in offspring at P28. Moreover, lithium mitigated the sevoflurane-induced reduction in Pax6, Ccnd1 and neurogenesis. All these results suggest that multiple sevoflurane exposure may induce detrimental effects in the developing brains of fetus and offspring by the depression of neurogenesis through Pax6 pathway.
七氟醚广泛应用于孕妇的非产科手术，但其对胎儿大脑的影响仍不完全清楚。我们着手评估多次母体暴露于七氟醚对胎儿及子代神经发生和认知功能障碍的影响。怀孕小鼠（妊娠第15.5天）和培养的小鼠神经干细胞（NSCs）连续三天每天暴露于七氟醚（分别为2.5%×2小时和4.1%×2小时）。通过莫里斯水迷宫测定子代的认知功能。通过免疫荧光、蛋白质印迹和定量聚合酶链反应分析胎儿大脑和神经干细胞中Ccnd1和Pax6的表达。通过BrdU染色评估神经发生。结果表明，怀孕小鼠多次暴露于七氟醚会导致Pax6和Ccnd1表达降低、神经干细胞增殖和胎儿海马神经发生受到抑制，这可能导致子代在出生后第28天学习和记忆受损。此外，锂减轻了七氟醚诱导的Pax6、Ccnd1和神经发生的减少。所有这些结果表明，多次暴露于七氟醚可能通过Pax6途径抑制神经发生，从而对胎儿和子代发育中的大脑产生有害影响。
