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Desflurane and Surgery Exposure During Pregnancy Decrease Synaptic Integrity and Induce Functional Deficits in Juvenile Offspring Mice.
Neurochemical Research ( IF 4.4 ) Pub Date : 2019-12-20 , DOI: 10.1007/s11064-019-02932-z
Shanshan Zou 1, 2 , Zheng Zachory Wei 3 , Yun Yue 1 , Hui Zheng 2 , Michael Qize Jiang 3 , Anshi Wu 1
Affiliation  

Anesthesia in pregnant women may cause adverse effects in the hippocampus of unborn babies and fetal brain development. The mechanisms underlying pathological changes resulting from anesthetics are unclear. This study tested the hypothesis that exposure to desflurane during pregnancy may impair cognition and memory functions of juvenile offspring. Pregnant mice (at gestational day 14) were administered 10% desflurane for 3 h and compared to sham control and sciatic nerve hemi-transection surgery. Hippocampal tissues of both fetal (G14) and offspring mice (postnatal day 31) were collected and analyzed by real-time qPCR and Western blot. Functional tests were performed to assess fear and memory functions in offspring mice. Primary hippocampal neuronal cultures from postnatal day 0 (without desflurane exposure) were examined for neuronal and synaptic development under desflurane treatment in vitro. In this acute experiment, we showed that neuronal cultures exposed to desflurane significantly increased interleukin (IL)-6 expression and apoptotic gene caspase-3 activation. Desflurane exposure significantly reduced PSD-95 expression in hippocampal neurons. Similar changes were observed in hippocampal tissues from juvenile offspring mice. Inhaled desflurane impaired memory functions in offspring mice compared to sham control. These mice displayed higher sensitivity to fear conditioning. Neurons isolated from the mice exposed to desflurane exhibited significantly lower levels of synaptophysin expression. These results suggest that anesthetic exposure together with surgery during pregnancy may induce detrimental effects in juvenile offspring mice via the induction of cell death and disruption of synaptic integrity.

中文翻译:

怀孕期间的地氟醚和手术暴露会降低幼仔小鼠的突触完整性并导致功能缺陷。

孕妇麻醉可能会对未出生婴儿的海马和胎儿大脑发育产生不良影响。麻醉引起的病理变化的机制尚不清楚。这项研究检验了以下假设:怀孕期间暴露于地氟醚可能会损害幼仔的认知和记忆功能。妊娠小鼠(在妊娠第14天)给予10%地氟醚3 h,并与假对照和坐骨神经半横切手术进行比较。收集胎儿(G14)和后代小鼠(出生后第31天)的海马组织,并通过实时qPCR和Western印迹进行分析。进行功能测试以评估后代小鼠的恐惧和记忆功能。从出生后第0天开始的海马神经元培养物(无地氟醚暴露)在体外进行了地氟醚处理后检查了神经元和突触的发育。在这个急性实验中,我们显示了暴露于地氟醚的神经元培养物显着增加了白介素(IL)-6的表达和凋亡基因caspase-3的激活。地氟烷暴露显着降低海马神经元中PSD-95的表达。在幼仔后代的海马组织中观察到类似的变化。与假对照组相比,吸入地氟醚会损害后代小鼠的记忆功能。这些小鼠对恐惧条件表现出更高的敏感性。从暴露于地氟烷的小鼠中分离出的神经元表现出明显较低的突触素表达水平。
更新日期:2019-12-20
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