七氟醚麻醉降低了海马钙结合蛋白和突触后致密蛋白95的水平
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Sevoflurane Reduces Levels of Hippocalcin and Postsynaptic Density Protein 95
背景与目的
七氟醚是儿童常用的吸入麻醉剂,已证明能增加胞浆内钙离子含量,并导致幼龄小鼠的认知障碍。然而,由七氟醚诱发的胞浆内钙离子水平升高的下游后果,以及认知障碍的上游机制,仍很大程度上不确定。海马钙结合蛋白是一种神经元钙感受器蛋白,它与突触后密度蛋白95(PSD-95)结合。因此,我们着手确定七氟醚对体外和体内海马钙结合蛋白和PSD-95的影响。
方 法
小鼠和6日龄小鼠的海马神经元分别以4.1%的七氟醚处理6h或3%的七氟醚处理3天每天 2 h。然后我们测量海马钙结合蛋白和PSD-95的水平,并评估BAPTA,一种细胞内钙离子螯合物,以及NMDA受体的部分拮抗剂剂——美金刚,它可以抑制七氟醚的效果。
结 果
我们发现,七氟醚麻醉后立即降低了神经元中海马钙结合蛋白和PSD-95的水平;小鼠海马体内海马和PSD-95的水平,但在麻醉后三周只有PSD-95水平降低。BAPTA抑制了七氟醚对神经元的影响。美金刚减弱了七氟醚胺降低海马钙结合蛋白和PSD-95水平的影响,以及七氟醚-诱发的小鼠认知障碍。
结 论
七氟醚降低了海马钙结合蛋白和PSD-95的水平,这可能是由七氟醚-诱发的胞浆内钙离子升高和七氟醚-诱发的认知障碍之间的桥梁机制之一。
原始文献摘要
Jie Z, Dong Y, Chen Z, et al. Anesthetic Sevoflurane Reduces Levels of Hippocalcin and Postsynaptic Density Protein 95[J]. Molecular Neurobiology, 2015, 51(3):853.
Abstract: Sevoflurane, the commonly used inhalation anesthetic in children, has been shown to enhance cytosolic calcium levels and induce cognitive impairment in young mice. However, the downstream consequences of the sevoflurane-induced elevation in cytosolic calcium levels and the upstream mechanisms of the sevoflurane-induced cognitive impairment remain largely to be determined. Hippocalcin is one of the neuronal calcium sensor
proteins, and also binds to postsynaptic density protein 95 (PSD-95). We therefore set out to determine the effects of sevoflurane on the levels of hippocalcin and PSD-95 in vitro and in vivo.Hippocampus neurons from mice and 6-day-old mice were treated with 4.1%sevoflurane for 6 h or
3%sevoflurane 2 h daily for 3 days, respectively. We then measured the levels of hippocalcin and PSD-95, and assessed whether BAPTA, an intracellular
calcium chelator, and memantine, a partial antagonist of the NMDAreceptor, could inhibit the sevoflurane’s effects.We found that sevoflurane decreased the levels of hippocalcin and PSD-95 in the neurons; and decreased the levels of hippocalcin and PSD-95 in the hippocampus of mice immediately after
the anesthesia, but only the PSD-95 levels three weeks after the anesthesia. BAPTA inhibited the sevoflurane’s effects in the neurons. Memantine attenuated the sevoflurane-induced reductions in the levels of hippocalcin and PSD-95, as well as the sevoflurane-induced cognitive impairment in mice. These data suggested that sevoflurane decreased the levels of hippocalcin and PSD-95, which could serve as one of bridge mechanisms between the sevoflurane-induced elevation of cytosolic calcium levels and the sevoflurane-induced cognitive impairment.
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