Condorelli D F, Belluardo N, Mudò G, Dell'Albani P, Jiang X, Giuffrida-Stella A M
Institute of Biochemistry, School of Medicine, University of Catania, Italy.
Neurochem Int. 1994 Oct;25(4):367-76. doi: 10.1016/0197-0186(94)90144-9.
In the present investigation we address the question of whether one of the responses to increased neuronal activity is a modification of the expression of the different subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-selective glutamate receptors (GluR-1, GluR-2, GluR-3). Thus, we used two different models of generalized status epilepticus, as widespread elevated neuronal activity, to study in vivo responses of the AMPA receptor mRNA expression in rat forebrain. By Northern blot analysis and in situ hybridization, we show that one of the delayed responses to LiCl/pilocarpine-induced status epilepticus is a dramatic change in the mRNA level of some subunits of AMPA-selective glutamate receptors. These effects, which appear between 6 and 12 h after the drug treatment, are subunit and brain region specific. The most striking example of differential expression of the three examined GluR mRNAs can be observed in the dentate gyrus of the hippocampus. In this specific brain subregion an increase of GluR-3 mRNA level is induced 12 h after LiCl/pilocarpine treatment, while a clear decrease in GluR-1 mRNA level and no significant change in GluR-2 mRNA level can be observed in the same area under these experimental conditions. Both the GluR-1 decrease and the GluR-3 increase are transient effects and a return to basal level can be observed after 48-72 h. In the CA1 layer of the hippocampus, a parallel decrease of both GluR-1 and GluR-3 expression is found 12-24 h after drug treatment, followed by a recovery of the expression to control values at 48 h. In kainate-induced epilepsy we could reproduce the late increase (12-24 h) in GluR-3 mRNA in the dentate gyrus; however, under this experimental condition, no clear decrease of GluR-1 expression can be observed in this area. A general decrease in mRNA level for the AMPA receptor subunits (GluR-1-3) in the hippocampal layers, in particular in CA3 and CA4 subfields, was also observed. In conclusion the results reported in the present paper reveal a specific regulation of GluR gene expression in the granule cells of the hippocampal dentate gyrus and stimulate further investigation on the functional role of the GluR-3 subunit in the receptor-channel complex.
在本研究中，我们探讨了神经元活动增加的一种反应是否是α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）选择性谷氨酸受体（GluR-1、GluR-2、GluR-3）不同亚基表达的改变。因此，我们使用两种不同的全身性癫痫持续状态模型，作为广泛升高的神经元活动，来研究大鼠前脑AMPA受体mRNA表达的体内反应。通过Northern印迹分析和原位杂交，我们表明，对氯化锂/毛果芸香碱诱导的癫痫持续状态的延迟反应之一是AMPA选择性谷氨酸受体某些亚基的mRNA水平发生显著变化。这些效应在药物治疗后6至12小时出现，具有亚基和脑区特异性。在所检测到的三种GluR mRNA差异表达的最显著例子可在海马齿状回中观察到。在这个特定的脑亚区域，氯化锂/毛果芸香碱治疗12小时后诱导GluR-3 mRNA水平升高，而在这些实验条件下，同一区域可观察到GluR-1 mRNA水平明显下降，GluR-2 mRNA水平无显著变化。GluR-1的下降和GluR-3的升高都是短暂效应，48 - 72小时后可观察到恢复到基础水平。在海马的CAI层，药物治疗后12 - 24小时发现GluR-1和GluR-3表达平行下降，随后在48小时恢复到对照值。在海藻酸诱导的癫痫中，我们可以重现齿状回中GluR-3 mRNA的后期升高（12 - 24小时）；然而，在这种实验条件下，该区域未观察到GluR-1表达明显下降。还观察到海马层中AMPA受体亚基（GluR-1 - 3）的mRNA水平普遍下降，特别是在CA3和CA4亚区。总之，本文报道的结果揭示了海马齿状回颗粒细胞中GluR基因表达的特定调节，并激发了对GluR-3亚基在受体-通道复合物中的功能作用的进一步研究。
