Department of Anesthesiology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, China.
Neurochem Res. 2020 Jul;45(7):1626-1635. doi: 10.1007/s11064-020-03023-0. Epub 2020 Apr 13.
Repeated or prolonged use of general anesthetics in pregnant women may disturb the neurodevelopment of infants. Compelling evidence indicates that maternal exercise during pregnancy has positive effects on the cognitive function of offspring. We previously confirmed the preventive potential of maternal treadmill training for cognitive deficits induced by in utero exposure to sevoflurane in rat pups. However, the underlying mechanism(s) needed further clarification. Thus, the aim of the present study was to investigate the effects of maternal exercise on the epigenetic regulation of genes linked to brain plasticity and function. Pregnant rats on gestational day 13 (GD 13) received 2 h of 3% sevoflurane or 30% oxygen daily on three consecutive days (GD 13-15). Pregnant rats in the exercise groups were forced to run on a treadmill for 60 min/day, 5 days/week, for a duration of 3 weeks. On postnatal day 0 (PND 0), the brains of rat pups were harvested for biochemical and histochemical studies. On PNDs 28-33, the learning and memory ability of rat pups was assessed using Morris water maze task. Maternal exercise ameliorated sevoflurane-induced decreases in p300 histone acetyltransferase (HAT) expression and inhibition of BDNF signaling. Maternal exercise improved performance in the Morris water maze task. However, these effects were reversed by p300 inhibitor. Our results indicated that maternal treadmill exercise during pregnancy can ameliorate cognitive dysfunction induced by prenatal sevoflurane exposure; p300 HAT-mediated BDNF signaling activation might contribute to the neuroprotective effects of maternal exercise.
孕妇重复或长时间使用全身麻醉药可能会干扰婴儿的神经发育。有力证据表明，孕妇在怀孕期间进行运动对后代的认知功能有积极影响。我们之前已经证实，母体跑步机训练可预防子宫内接触七氟醚对幼鼠认知功能的损害。然而，其潜在机制仍需要进一步阐明。因此，本研究旨在探讨母体运动对与脑可塑性和功能相关基因的表观遗传调控的影响。妊娠第 13 天（GD 13）的大鼠接受 3%七氟醚或 30%氧气 2 小时，每天连续 3 天（GD 13-15）。运动组的孕鼠每天在跑步机上强制运动 60 分钟，每周 5 天，持续 3 周。在产后第 0 天（PND 0），收获幼鼠的大脑进行生化和组织化学研究。在 PND 28-33 时，使用 Morris 水迷宫任务评估幼鼠的学习和记忆能力。母体运动改善了七氟醚诱导的 p300 组蛋白乙酰转移酶（HAT）表达减少和 BDNF 信号抑制。母体运动改善了 Morris 水迷宫任务中的表现。然而，这些作用被 p300 抑制剂逆转。我们的结果表明，妊娠期间母体跑步机运动可以改善产前七氟醚暴露引起的认知功能障碍；p300 HAT 介导的 BDNF 信号激活可能是母体运动的神经保护作用的原因。
