Changes in glutamate receptor subunit composition in hippocampus and cortex in patients with refractory epilepsy
Changes in glutamate receptor subunit composition in hippocampus and cortex in patients with refractory epilepsy
复制标题
DOI：
10.1016/s0022-510x(97)00180-9
复制
发表时间：
1997-12-09
影响因子：
4.4
通讯作者：
Deadwyler, SA
中科院分区：
文献类型：
--
作者：
Grigorenko, E;Glazier, S;Deadwyler, SA
对难治性癫痫患者的海马区和颞叶皮质谷氨酸受体亚单位谱进行了评估。用逆转录(RT)和聚合酶链式反应(PCR)进行分子生物学分析，发现难治性癫痫患者的海马区和皮质组织中AMPA/KA谷氨酸受体亚单位的转录本的分布发生了变化，与6例人类和4例无癫痫史或癫痫药物治疗的非人类灵长类动物的类似组织相比。在癫痫患者400 mm的海马区，GluR1亚单位的信使核糖核酸严重减少(对照的38%)。在相同受试者的切除的颞叶皮质样本中，GluR1亚单位的表达没有那么严重，但显著减少(对照的54%)。GluR4亚单位在海马区的表达水平也显著降低(对照组的68%)，但与GluR1相反，在颞叶皮质中GluR4的表达水平并未降低。癫痫组大鼠海马区和皮质组织中GluR2基因的表达水平与对照组相比无明显变化。通过Western印迹分析量化的GluR1和GluR4亚基的蛋白水平也在癫痫患者的海马区和皮质组织中降低。另外两个红藻氨酸亚单位转录本，GluR6和KA1也显示出与非癫痫组织(分别为对照的136%和71%)相比的显著变化。结果讨论了可能的机制，通过延长癫痫发作可能导致某些AMPA/KA亚单位选择性丢失。(C)1997年爱思唯尔科学公司。
An assessment of glutamate receptor subunit profiles was made in hippocampus and temporal lobe cortex of patients with refractory epilepsy. Molecular biological analyses using reverse transcription reaction (RT) followed by polymerase chain reaction (PCR) revealed changes in the distribution profile of the transcripts of AMPA/KA glutamate receptor subunits in hippocampal and cortical tissue from patients with refractory epilepsy when compared to similar tissue from six human and four non-human primate samples with no history of seizures or seizure medication. A severe mean decrease (38% of control) in mRNA for the GluR1 subunit was found in 400 mm cross-sections of hippocampus from patients with epilepsy. Less severe but significant reductions in that GluR1 subunit expression (54% of control) were exhibited in samples of excised temporal pole cortex from the same subjects. Message for the GluR4 subunit was also significantly decreased in hippocampus (68% of control), but in contrast to GluR1, GluR4 mRNA level was not decreased in temporal cortex. Levels of GluR2 mRNA were not significantly changed in epileptic hippocampal and cortical tissue relative to control samples. Protein levels of the GluR1 and GluR4 subunits quantified by Western blot analysis were also reduced in hippocampal and cortical tissue from epilepsy patients. Two other kainate subunit transcripts, GluR6 and KA1 also showed significant changes compared to non-epileptic tissue (136% and 71% of control, respectively). Results are discussed in terms of possible mechanisms by which protracted seizures could produce selective loss of certain AMPA/KA subunits. (C) 1997 Elsevier Science B.V.