GABAB1a, GABAB1b, and GABAB2 mRNA variants expression in hippocampus resected from patients with temporal lobe epilepsy
GABAB1a, GABAB1b, and GABAB2 mRNA variants expression in hippocampus resected from patients with temporal lobe epilepsy
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DOI：
10.1016/j.neuroscience.2003.08.044
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Bowery, NG
中科院分区：
文献类型：
--
作者：
Princivalle, AP;Duncan, JS;Bowery, NG
本研究的目的是利用定量原位杂交自动放射成像技术，研究两种GABA（B1）受体亚型和GABA（B2）亚基在人死后对照海马切片和癫痫患者切除的切片中的mRNA表达。利用人类控制海马切片显示，所采用的寡核颗粒是特异性受体。将海马硬化症和颞叶癫痫患者的手术标本海马切片与神经功能正常的死后对照进行神经病理学和GABA(B) mRNA表达的比较。海马大部分亚区均有神经元丢失，但在枕下未见明显差异。GABA（B1a）和GABA（B1b）异构体mrna在人类对照海马切片中的定位支持并扩展了早期使用GABA（B1）泛探针的研究，该探针不能区分两种GABA（B1）异构体。此外，GABA(B2) mRNA的位置证实了受体的异二聚化。因此，尽管GABA（B1b）和GABA（B2）之间存在明显的相关性，但GABA（B1a）没有表现出这种相关性。GABA（B1b）和GABA（B2）表达强度相近，而GABA（B1a）杂交信号较低。对照和癫痫组海马不同亚区3种mrna的表达均有明显的减少或增加。GABA(B)亚型和每个剩余神经元亚基mRNA表达量在门脑和齿状回显著增加。这些结果表明，GABA(B)受体mRNA表达在人TLE中发生改变；观察到的变化可能也有助于抵消持续的过度兴奋性。(c) 2003年。Elsevier Ltd.出版。版权所有。
The aim of this study was to investigate the mRNA expression of the two GABA(B1) receptor isoforms and the GABA(B2) subunit, in human postmortem control hippocampal sections and in sections resected from epilepsy patients using quantitative in situ hybridisation auto radiography. Utilising human control hippocampal sections it was shown that the oligonucleoticles employed were specific to the receptor. Hippocampal slices from surgical specimens obtained from patients with hippocampal sclerosis and temporal lobe epilepsy were compared with neurologically normal postmortem control subjects for neuropathology and GABA(B) mRNA expression. Neuronal loss was observed in most of the hippocampal subregions, but in the subiculum no significant difference was detected.The localisation of GABA(B1a) and GABA(B1b) isoform mRNAs in human control hippocampal sections supported and extended earlier studies using the GABA(B1) pan probe, which does not distinguish between the two GABA(B1) isoforms. Moreover, the GABA(B2) mRNA location confirmed the heterodimerisation of the receptor. Thus, although there was an apparent correlation between GABA(B1b) and GABA(B2), GABA(B1a) exhibited no such relationship. GABA(B1b) and GABA(B2) showed a similar intensity of expression whilst GABA(B1a) displayed a lower hybridisation signal. Comparison of the expression of the three mRNAs between control and epileptic subjects showed significant decreases or increases in different hippocampal subregions.GABA(B) isoforms and subunit mRNA expression per remaining neuron was significantly increased in the hilus and dentate gyrus. These results demonstrate that altered GABA(B) receptor mRNA expression occurs in human TLE; possibly the observed changes may also serve to counteract ongoing hyperexcitability. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.