Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA 02129-2060, USA.
Curr Mol Med. 2013 Nov;13(9):1446-54. doi: 10.2174/15665240113139990073.
Recent population studies suggest that children who receive anesthesia and surgery could be at an increased risk for developing learning disabilities. The underlying reason for this clinical observation is largely unknown. Whether undergoing anesthesia contributes to learning disability development, or if the need for anesthesia and surgery is a marker for other unidentified factors that contribute to the development of learning disabilities, remains to be determined. Neurogenesis, regulated by the Wnt-catenin signaling pathway, has been shown to be involved in learning and memory, and sevoflurane is the most commonly used inhalation anesthetic in children. We therefore set out to determine the effects of sevoflurane on neurogenesis and the Wnt-catenin signaling pathway in mouse neural progenitor cells (NPCs) using immunofluorescence and Western blot analysis. Here we show for the first time that 4.1%, but not 2.0%, sevoflurane reduced mouse NPC proliferation, increased Glycogen synthase kinase-3β(GSK-3β) levels, and decreased levels of β-Catenin in mouse NPCs. The GSK-3β inhibitor Lithium attenuated the sevoflurane-induced reduction in mouse NPC proliferation. The data suggest that sevoflurane may reduce neurogenesis through the Wnt-catenin signaling pathway. These findings would promote further studies to investigate the effects of anesthesia on neurogenesis and function of learning and memory, as well as the underlying mechanisms in vitro and in vivo. Ultimately these efforts would lead to safer anesthesia care and better postoperative outcomes in children.
最近的人口研究表明，接受麻醉和手术的儿童可能面临更高的学习障碍风险。这种临床观察的根本原因在很大程度上是未知的。是麻醉本身导致学习障碍的发展，还是需要麻醉和手术是导致学习障碍发展的其他未识别因素的标志物，仍有待确定。神经发生受 Wnt-连环蛋白信号通路调控，已被证明与学习和记忆有关，七氟醚是儿童最常用的吸入麻醉剂。因此，我们使用免疫荧光和 Western blot 分析来确定七氟醚对小鼠神经祖细胞 (NPC) 中的神经发生和 Wnt-连环蛋白信号通路的影响。在这里，我们首次表明 4.1%，而不是 2.0%的七氟醚可降低小鼠 NPC 的增殖，增加糖原合酶激酶-3β（GSK-3β）水平，并降低小鼠 NPC 中的β-连环蛋白水平。GSK-3β抑制剂锂可减弱七氟醚诱导的小鼠 NPC 增殖减少。数据表明，七氟醚可能通过 Wnt-连环蛋白信号通路减少神经发生。这些发现将促进进一步的研究，以调查麻醉对神经发生和学习记忆功能的影响，以及体外和体内的潜在机制。最终，这些努力将导致儿童更安全的麻醉护理和更好的术后结果。
