Porter R H, Burnet P W, Eastwood S L, Harrison P J
University Department of Psychiatry, Warneford Hospital, Oxford, UK.
Brain Res. 1996 Feb 26;710(1-2):97-102. doi: 10.1016/0006-8993(95)01377-6.
Kainate-preferring glutamate receptors may contribute to the glutamatergic responses to seizures. The cloning of their encoding genes overcomes limitations of the receptor ligands available for their investigation. We have examined the expression of the high affinity kainate receptor subunits KA1 and KA2 mRNAs in the rat hippocampus, using electroconvulsive shock (ECS) as a seizure paradigm not confounded by neurotoxicity. A single shock reduced the levels of KA1 mRNA in the CA3c region, while increasing the expression of KA2 mRNA in the dentate gyrus. Following repeated ECS (5 shocks over 10 days), KA1 mRNA was reduced in CA3c and in CA3a-b but was unchanged in dentate gyrus. KA2 mRNA, on the other hand, significantly increased in dentate gyrus, and to a lesser extent in CA3c and CA1. All changes in KA1 and KA2 mRNAs had returned to baseline 3 weeks after the last shock. We also measured the expression of cyclophilin mRNA, and found it to be reduced in all hippocampal subfields, and in the parietal cortex, after a single ECS. It returned to control levels after repeated ECS but was again reduced following 3 weeks recovery from repeated ECS. These results indicate that the expression of KA1 and KA2 not only change in opposite directions in the rat hippocampus after ECS, but that the alterations are anatomically and temporally regulated. In the respect that cyclophilin is regarded as a housekeeping gene, the reduction in its mRNA suggests that ECS may have more persistent and widespread effects on brain gene expression than previously suspected.
红藻氨酸受体亚型可能参与了癫痫发作时的谷氨酸能反应。其编码基因的克隆克服了用于研究的受体配体的局限性。我们使用电休克（ECS）作为一种不受神经毒性干扰的癫痫发作模型，检测了大鼠海马体中高亲和力红藻氨酸受体亚基KA1和KA2 mRNA的表达。单次电休克降低了CA3c区KA1 mRNA的水平，同时增加了齿状回中KA2 mRNA的表达。反复进行电休克（10天内5次）后，CA3c区和CA3a - b区的KA1 mRNA减少，但齿状回中未发生变化。另一方面，KA2 mRNA在齿状回中显著增加，在CA3c区和CA1区增加程度较小。最后一次电休克3周后，KA1和KA2 mRNA的所有变化均恢复到基线水平。我们还测量了亲环蛋白mRNA的表达，发现单次电休克后，所有海马亚区和顶叶皮质中的该mRNA均减少。反复电休克后其恢复到对照水平，但在反复电休克后3周恢复时再次减少。这些结果表明，电休克后大鼠海马体中KA1和KA2的表达不仅呈相反方向变化，而且这些变化在解剖学和时间上受到调节。鉴于亲环蛋白被视为一种管家基因，其mRNA的减少表明电休克对脑基因表达的影响可能比以前认为的更持久、更广泛。
