CHANGES IN GLUTAMATE-RECEPTOR AND PROENKEPHALIN GENE-EXPRESSION AFTER KINDLED SEIZURES
CHANGES IN GLUTAMATE-RECEPTOR AND PROENKEPHALIN GENE-EXPRESSION AFTER KINDLED SEIZURES
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DOI：
10.1016/0169-328x(94)90115-5
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发表时间：
1994-07-01
期刊：
影响因子：
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通讯作者：
CHRISTAKOS, S
中科院分区：
文献类型：
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作者：
LEE, S;MISKOVSKY, J;CHRISTAKOS, S
点燃癫痫后基因表达的变化通过对离散脑区的显微解剖以及Northern和Slot印迹分析来检测。实验动物采用两种方案中的任何一种：(1)通过海马区电极每30min给予50 Hz/10个S刺激序列(隔日12次，共4天)；(2)传统方法，给予50 Hz/10个S刺激序列，每天3次，共16天。在最后一次点燃发作后24小时或30天处死大鼠。我们首先研究了点燃可能影响神经递质受体mRNA转录的可能性。我们发现在快速点燃后24小时，海马区、杏仁核/内嗅觉皮质和额顶皮质AMPA/海人藻酸激活的谷氨酸受体mRNAs(GluR1、-2、-3mRNAs)显著减少(22-58%)，但不是30天。而GABA受体α(1)、α(2)、α(4)或β(1)mRNAs在传统点燃后30天或快速点燃后24小时的脑区均未见明显变化。此外，我们还检测了点燃后脑啡肽原表达的变化。快速点燃后24小时，额顶叶皮质、海马区和杏仁核/内嗅区前脑啡肽原基因表达显著增加(1.7~10倍)，但30天后无明显变化。我们的研究结果表明，谷氨酸受体和脑啡肽原基因表达的变化是点燃癫痫的强烈、急性后遗症，可能与点燃有关。
Changes in gene expression after kindled seizures were examined using microdissection of discrete brain areas and Northern and slot blot analyses. Experimental animals were kindled with either of two protocols: (1) a paradigm in which 50 Hz/10 s stimulus trains were delivered every 30 min through hippocampal electrodes (12 stimulations every other day for 4 days) and (2) a traditional approach in which 50 Hz/10 s stimulus trains were given to the hippocampus three times daily for 16 days. Rats were sacrificed 24 h or 30 days after the last kindled seizure. We first examined the possibility that kindling may affect transcription of mRNA for neurotransmitter receptors. We found significant decreases (22-58%) in AMPA/kainate activated glutamate receptor mRNAs (GluR1, -2, -3 mRNAs) in hippocampus, amygdala/entorhinal cortex and in frontoparietal cortex 24 h but not 30 days after rapidly kindled seizures. However, changes in GABA receptor alpha(1), alpha(2), alpha(4) Or beta(1) mRNAs were net observed in any brain region 30 days after traditional kindling or 24 h after rapidly kindled seizures. In addition, we tested whether changes in the expression of proenkephalin could be detected after kindling. We found significant increases (1.7-10 fold) in proenkephalin mRNA in the frontoparietal cortex, hippocampus and in the amygdala/entorhinal cortex 24 h but not 30 days after rapidly kindled seizures. Our findings suggest that changes in glutamate receptor and proenkephalin gene expression are robust, acute sequelae to kindled seizures and may be involved in kindling.