Status epilepticus decreases glutamate receptor 2 mRNA and protein expression in hippocampal pyramidal cells before neuronal death.
Status epilepticus decreases glutamate receptor 2 mRNA and protein expression in hippocampal pyramidal cells before neuronal death.
复制标题
癫痫持续状态在神经元死亡前会降低海马锥体细胞中谷氨酸受体 2 mRNA 和蛋白的表达。
DOI：
10.1073/pnas.97.7.3631
复制
发表时间：
2000
影响因子：
11.1
通讯作者：
Zukin,RS
中科院分区：
文献类型：
--
作者：
Grooms,SY;Opitz,T;Bennett,MV;Zukin,RS
海人酸（KA）诱导的癫痫持续状态在成年大鼠中导致海马CA 1和CA 3区锥体神经元的延迟性、选择性死亡。原位杂交、免疫标记和定量Western印迹显示，死亡前CA 1和CA 3中谷氨酸受体2（GluR 2）mRNA和蛋白（限制α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体Ca 2+渗透性的亚基）下调。GluR 1 mRNA和蛋白在细胞死亡前没有变化或略有增加。这些变化可能导致形成GluR 2缺乏，Ca 2+渗透AMPA受体和内源性谷氨酸的毒性增加。GluR 2免疫标记在齿状回的颗粒细胞中是不变的，这些颗粒细胞对癫痫诱导的死亡具有抵抗力。因此，钙渗透AMPA受体的形成可能是癫痫持续状态后迟发性神经变性的关键介质。
Kainic acid (KA)-induced status epilepticus in adult rats leads to delayed, selective death of pyramidal neurons in the hippocampal CA1 and CA3. Death is preceded by down-regulation of glutamate receptor 2 (GluR2) mRNA and protein [the subunit that limits Ca2+permeability of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors] in CA1 and CA3, as indicated byin situhybridization, immunolabeling, and quantitative Western blotting. GluR1 mRNA and protein are unchanged or slightly increased before cell death. These changes could lead to formation of GluR2-lacking, Ca2+-permeable AMPA receptors and increased toxicity of endogenous glutamate. GluR2 immunolabeling is unchanged in granule cells of the dentate gyrus, which are resistant to seizure-induced death. Thus, formation of Ca2+-permeable AMPA receptors may be a critical mediator of delayed neurodegeneration after status epilepticus.