Prenatal sevoflurane exposure causes abnormal development of the entorhinal cortex in rat offspring
Prenatal sevoflurane exposure causes abnormal development of the entorhinal cortex in rat offspring
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产前七氟醚暴露导致大鼠后代内嗅皮质发育异常
DOI：
10.31083/j.jin2003065
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发表时间：
2021-09-30
影响因子：
1.8
通讯作者：
Song, Xingrong
中科院分区：
文献类型：
--
作者：
Gao, Ying;Zhao, Tianyun;Song, Xingrong
作为γ-氨基丁酸A型受体激动剂，七氟烷是麻醉中常用的全身麻醉剂，影响后代的神经发育。我们假设七氟烷可以通过妊娠中期内嗅皮质（ECT）中的神经调节蛋白-1-表皮生长因子受体-4（NRG1-ErbB4）通路调节中间神经元。将6只妊娠中期(妊娠14.5天)雌性大鼠随机均分为七氟醚(SeV)组和对照组。 SeV组大鼠暴露于4%七氟醚3小时。通过免疫组化检测子代NRG1和ErbB4、小白蛋白（PV）和谷氨酸脱羧酶（GAD67）以及N-甲基-D-天冬氨酸受体亚基2A（NR2A）和亚基2B（NR2B）的表达水平。通过高尔基染色检查 ECT 中的锥体神经元。 SeV组的NRG1和ErbB4水平显着降低（P < 0.01），PV和GAD67（中间神经元）水平降低（P < 0.01）。 SeV 组中 NR2B 水平升高，而 NR2A 水平降低（P < 0.01）。 SeV组锥体神经元发育异常（P < 0.05）。总之，产前七氟醚暴露可能通过激活NRG1-ErbB4通路导致中间神经元紊乱，从而导致妊娠中期锥体神经元发育异常。妊娠中期产前接触七氟醚可能对大鼠后代的神经发育造成潜在危害。该研究可能揭示七氟醚对大鼠后代影响机制的新途径。
As a gamma-aminobutyric acid type A receptor agonist sevoflurane is a common general anesthetic used in anesthesia and affects the neural development in offspring. We hypothesized that sevoflurane could regulate interneurons via the neuregulin-1-epidermal growth factor receptor-4 (NRG1-ErbB4) pathway in the entorhinal cortex (ECT) of the middle pregnancy. Six female rats in middle pregnancy (14.5 days of pregnancy) were randomly and equally divided into sevoflurane (SeV) and control groups. The rats in the SeV group were exposed to 4% sevoflurane for 3 hours. The expression levels of NRG1 and ErbB4, parvalbumin (PV) and glutamic acid decarboxylase (GAD67), and N-methyl-D-aspartate receptor subunit 2A (NR2A) and subunit 2B (NR2B) in offspring were examined through immunohistochemistry. The pyramidal neurons in the ECT were examined via Golgi staining. The levels of NRG1 and ErbB4 were significantly decreased (P < 0.01) and the levels of PV and GAD67 (interneurons) were found to be decreased in the SeV group (P < 0.01). The level of NR2B was found to be increased while the level of NR2A being decreased in the SeV group (P < 0.01). The development of pyramidal neurons was abnormal in the SeV group (P < 0.05). Conclusively, prenatal sevoflurane exposure could lead to the disturbance of the interneurons by activating the NRG1-ErbB4 pathway and subsequently result in abnormal development of pyramidal neurons in middle pregnancy. Prenatal sevoflurane exposure in middle pregnancy could be potentially harmful to the neural development of rat offspring. This study may reveal a novel pathway in the influence mechanism of sevoflurane on rat offspring.