Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin 300052, China.
Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin 300052, China.
Brain Res. 2019 May 1;1710:188-198. doi: 10.1016/j.brainres.2018.12.010. Epub 2018 Dec 7.
In recent years, the neurotoxicity of general anesthetics in the developing brain has been studied and raised great concern as a major health issue to the public and physicians. Sevoflurane inhalation may induce neurotoxicity expressed as memory and learning impairment in young animals. In the current study, we investigated the role of nectin-1 and corticotrophin-releasing hormone receptor type 1 (CRHR1) in sevoflurane-induced learning deficits and dendritic spines loss in neonatal mice. Neonatal mice (P7) were treated with 3% sevoflurane with 60% O or 60% O for 6 h. Cognitive function was evaluated by Y Maze, Object recognition test, and Morris Water Maze. Hippocampal nectin-1 and L-afadin expression assessed using western blot analysis. The dendritic spines morphology of the hippocampus was determined using Golgi impregnation on 7 d and 2 months old. Sevoflurane exposed to neonatal mice decreased hippocampal nectin-1 levels from 1 h to 2 months after sevoflurane inhalation and attenuated working and spatial memory and spinal number in adulthood, which could be reversed by nectin-1 overexpression and CRHR1 antagonist Antalarmin. Nectin-1 knockdown caused spatial learning deficits and dendritic spine loss and lower L-afadin protein expression. Sevoflurane-induced nectin-1 and L-afadin expression decrease was mediated by CRHR1 signaling in the hippocampus. This information can be used to develop targeted intervention aimed at decreasing the neurotoxicity of sevoflurane inhalation.
近年来，全身麻醉药在发育中的大脑中的神经毒性已被研究，并引起了公众和医生的极大关注，成为一个主要的健康问题。七氟醚吸入可能会导致年轻动物的记忆和学习障碍等神经毒性。在本研究中，我们研究了 nectin-1 和促肾上腺皮质激素释放激素受体 1（CRHR1）在七氟醚诱导的新生小鼠学习能力下降和树突棘丢失中的作用。用 3%七氟醚与 60%氧气或 60%氧气处理 P7 新生小鼠 6 h。通过 Y 迷宫、物体识别试验和 Morris 水迷宫评估认知功能。使用 Western blot 分析评估海马 nectin-1 和 L-afadin 的表达。使用高尔基浸渍法在 7 天和 2 个月大时确定海马的树突棘形态。七氟醚暴露于新生小鼠中，从七氟醚吸入后 1 h 到 2 个月降低了海马 nectin-1 水平，并减弱了成年后的工作记忆和空间记忆以及棘突数量，而 nectin-1 过表达和 CRHR1 拮抗剂 Antalarmin 可逆转这种情况。Nectin-1 敲低导致空间学习能力下降和树突棘丢失以及 L-afadin 蛋白表达降低。海马中 CRHR1 信号介导了七氟醚诱导的 nectin-1 和 L-afadin 表达减少。这些信息可用于开发旨在降低七氟醚吸入神经毒性的靶向干预措施。
