Role of GABA(A) receptor depolarization-mediated VGCC activation in sevoflurane-induced cognitive impairment in neonatal mice.
Role of GABA(A) receptor depolarization-mediated VGCC activation in sevoflurane-induced cognitive impairment in neonatal mice.
复制标题
GABAA 受体去极化介导的 VGCC 激活在七氟烷诱导的新生小鼠认知障碍中的作用
DOI：
10.3389/fncel.2022.964227
复制
发表时间：
2022
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
在新生小鼠中，七氟烷麻醉使GABA A型受体（GABAAR）去极化，导致认知障碍。钙在神经元中的积聚可导致神经毒性。电压门控钙通道（VGCC）可在异氟醚和缺氧条件下增加细胞内钙浓度。其潜在机制在很大程度上仍不清楚。用3%七氟烷麻醉6日龄小鼠，每天2小时，持续3天。采用Y-迷宫、新物体识别（NOR）试验、巴恩斯迷宫试验、免疫测定、免疫印迹、TUNEL试验和Golgi-Cox染色来评估小鼠和HT 22细胞中海马神经细胞的认知、钙浓度、炎症反应、GABAAR活化、VGCC表达、凋亡和增殖。与对照组相比，七氟烷组小鼠的认知功能受损。七氟醚组海马神经元Gabrb 3和Cav1.2表达增加（p < 0.01），钙离子浓度升高（p <0.01），神经元炎症反应和凋亡增加（p <0.01），DG区神经元增殖减少（p <0.01），树突棘密度降低（p < 0.05）。然而，Gabrb 3和Cav1.2的抑制减轻了认知障碍并降低了神经毒性。七氟烷通过诱导GABAAR去极化激活VGCC，导致认知障碍。活化的VGCC引起细胞内钙浓度增加和炎症反应，导致神经毒性和认知障碍。
In neonatal mice, anesthesia with sevoflurane depolarizes the GABA Type A receptor (GABAAR), which leads to cognitive impairment. Calcium accumulation in neurons can lead to neurotoxicity. Voltage-gated calcium channels (VGCCs) can increase intracellular calcium concentration under isoflurane and hypoxic conditions. The underlying mechanisms remain largely unknown. Six-day-old mice were anesthetized with 3% sevoflurane for 2 h/day for 3 days. The Y-Maze, new object recognition (NOR) test, the Barnes maze test, immunoassay, immunoblotting, the TUNEL test, and Golgi–Cox staining were used to assess cognition, calcium concentration, inflammatory response, GABAAR activation, VGCC expression, apoptosis, and proliferation of hippocampal nerve cells in mice and HT22 cells. Compared with the control group, mice in the sevoflurane group had impaired cognitive function. In the sevoflurane group, the expression of Gabrb3 and Cav1.2 in the hippocampal neurons increased (p < 0.01), the concentration of calcium ions increased (p < 0.01), inflammatory reaction and apoptosis of neurons increased (p < 0.01), the proliferation of neurons in the DG area decreased (p < 0.01), and dendritic spine density decreased (p < 0.05). However, the inhibition of Gabrb3 and Cav1.2 alleviated cognitive impairment and reduced neurotoxicity. Sevoflurane activates VGCCs by inducing GABAAR depolarization, resulting in cognitive impairment. Activated VGCCs cause an increase in intracellular calcium concentration and an inflammatory response, resulting in neurotoxicity and cognitive impairment.
登录
查看更多内容
DOI：
10.1126/science.aaf5206
发表时间：
2016-09-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Oh WC;Lutzu S;Castillo PE;Kwon HB
通讯作者：
Kwon HB
影响因子：
4
作者：
Yamasaki-Mann M;Parker I
通讯作者：
Parker I
麻醉剂会伤害正在发育的人类大脑吗？
影响因子：
2.9
作者：
Lin, Erica P.;Lee, Jeong-Rim;Loepke, Andreas W.
通讯作者：
Loepke, Andreas W.
影响因子：
5.3
作者：
Nunez, Joseph L.;McCarthy, Margaret M.
通讯作者：
McCarthy, Margaret M.
影响因子：
4.7
作者：
Bernardi, Rick E.;Uhrig, Stefanie;Hansson, Anita C.
通讯作者：
Hansson, Anita C.