Tsunashima K, Schwarzer C, Kirchmair E, Sieghart W, Sperk G
Department of Pharmacology, University of Innsbruck, Austria.
Neuroscience. 1997 Oct;80(4):1019-32. doi: 10.1016/s0306-4522(97)00144-9.
Kainic acid-induced seizures in rats represent an established animal model for human temporal lobe epilepsy. The neuropathological sequelae include acute status epilepticus followed by neurodegeneration in the CA1 and CA3 sector of the Ammon's horn and of interneurons in the hilus of the dentate gyrus. After about three weeks spontaneous recurrent seizures become manifest. We investigated changes in messenger RNA expression of 13 GABA(A) receptor subunits in the hippocampus of rats in the initial phase (6 h, 12 h and 24 h) after acute kainic acid-induced status epilepticus and seizure-related neuronal cell damage during and after acquisition of spontaneous recurrent seizures (seven and 30 days after kainic acid injection). In the granule cell layer, initial (after 6 to 12 h) decreases in (alpha2, alpha3, alpha5, beta1, beta3, gamma2 and delta messenger RNAs (by about 25 to 50%) were accompanied by increases (by about 50%) in alpha1, alpha4, and beta2 messages. At later intervals (after seven to 30 days), expression of alpha2, alpha4, beta3 and gamma2 messenger RNAs recovered to control values, with alpha5 and delta messenger RNA still being reduced (by 15 and 40% below control levels, respectively). Concentrations of the transcripts encoding for alpha1, alpha3, beta1, beta2, became markedly enhanced (between 20 and 50% of controls). Within the pyramidal cell layers CA1 and CA3, decreases in alpha2, alpha4, alpha5, beta(1-3) and gamma2 messenger RNAs were detected after seven to 30 days, reflecting pronounced neurodegeneration in these areas. The alpha1 transcript was decreased in CA3 after 24 h and increased to control levels indicating compensatory up-regulation of this message after seven days. Messenger RNAs encoding for alpha3-, gamma1-, and gamma3-subunits were detected at rather low levels, alpha6 was not present in the hippocampus. Our data suggest a fast but transient change in the expression of messenger RNAs encoding for different subunits of the GABA(A) receptor in the granule cell layer of the dentate gyrus. This is followed by a lasting augmentation of messenger RNAs encoding different GABA(A) receptor subunits in the same cell layer indicating long-lasting GABAergic inhibition. Changes within the pyramidal cell layer are mostly determined by concomitant neurodegenerative processes.
海人酸诱导的大鼠癫痫发作是一种公认的人类颞叶癫痫动物模型。神经病理学后遗症包括急性癫痫持续状态，随后是海马角CA1和CA3区以及齿状回门区中间神经元的神经变性。大约三周后，自发复发性癫痫发作开始显现。我们研究了急性海人酸诱导的癫痫持续状态后初始阶段（6小时、12小时和24小时）大鼠海马中13种GABA(A)受体亚基信使RNA表达的变化，以及在自发复发性癫痫发作获得期间和之后（海人酸注射后7天和30天）与癫痫发作相关的神经元细胞损伤情况。在颗粒细胞层，初始阶段（6至12小时后），α2、α3、α5、β1、β3、γ2和δ信使RNA减少（约25%至50%），同时α1、α4和β2信使RNA增加（约50%）。在随后的时间段（7至30天后），α2、α4、β3和γ2信使RNA的表达恢复到对照值，α5和δ信使RNA仍减少（分别比对照水平低15%和40%）。编码α1、α3、β1、β2的转录本浓度显著增强（为对照值的20%至50%）。在锥体细胞层CA1和CA3内，7至30天后检测到α2、α4、α5、β(1 - 3)和γ2信使RNA减少，反映了这些区域明显的神经变性。α1转录本在24小时后在CA3中减少，7天后增加到对照水平，表明该信使RNA在7天后出现代偿性上调。编码α3、γ1和γ3亚基的信使RNA检测水平相当低，海马中不存在α6。我们的数据表明，齿状回颗粒细胞层中编码GABA(A)受体不同亚基的信使RNA表达发生快速但短暂的变化。随后，同一细胞层中编码不同GABA(A)受体亚基的信使RNA持续增加，表明存在持久的GABA能抑制。锥体细胞层内的变化主要由伴随的神经变性过程决定。
