Influence of hippocampal low-frequency stimulation on GABAA R α1, ICER and BNDF expression level in brain tissues of amygdala-kindled drug-resistant temporal lobe epileptic rats

Influence of hippocampal low-frequency stimulation on GABAA R α1, ICER and BNDF expression level in brain tissues of amygdala-kindled drug-resistant temporal lobe epileptic rats
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DOI:
10.1016/j.brainres.2018.08.013
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发表时间:
2018-11-01
期刊:
影响因子:
2.9
通讯作者:
Liu, Tao
Liu, Tao
中科院分区:
医学3区
文献类型:
--
作者:
Xu, Kaya;Liu, Zhaoyang;Liu, Tao

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本研究探讨了低频刺激(Hip-LFS)的治疗作用及其对A型氨基丁酸受体α1亚单位(GABA(A)Rα1亚单位)、诱导型cAMP早期抑制因子(ICER)和脑源性神经营养因子(BNDF)的影响。慢性电刺激杏仁核诱发癫痫模型。通过检测苯妥英钠和苯巴比妥对癫痫大鼠的癫痫发作反应,筛选耐药和药物敏感的癫痫大鼠。免疫组织化学和免疫印迹法检测大鼠脑内GABA(A)Rα1亚单位、ICER和BDNF表达的变化。耐药癫痫大鼠ICER和BDNF的表达水平明显升高,而GABA(A)Rα1亚单位的表达水平明显下降。而耐药癫痫大鼠经Hip-LFS治疗2周后,ICER、BDNF表达水平明显降低,GABA(A)Rα1亚单位表达显著增加。同时减轻癫痫发作程度,改善脑电活动。本研究表明ICER和BDNF的升高可能与耐药的发生有关。Hip-LFS对耐药癫痫大鼠的治疗作用可能与提高ICER和BDNF水平有关。
This study investigated the therapeutic effect of hippocampal low-frequency stimulation (Hip-LFS) and its influence on the type A gamma-aminobutyric acid receptor al subunit (GABA(A) R alpha 1 subunit), inducible cAMP early repressor (ICER) and brain-derived neurotrophic factors (BNDF). The model of epilepsy was induced by chronic electrical stimulation in amygdala. Drug-resistant and drug-sensitive epileptic rats were selected by testing their seizure response to phenytoin and phenobarbital. The changes of GABA(A) R alpha 1 subunit, ICER and BDNF expression were detected via immunohistochemistry and western blot. The expression levels of ICER and BDNF were increased remarkably but the GABA(A) R alpha 1 subunit decreased significantly in the drug-resistant epileptic rats. However, the expression levels of ICER, BDNF were decreased and the expression of the GABA(A) R alpha 1 subunit increased significantly in the drug-resistant epileptic rats after two weeks of Hip-LFS. Meanwhile, the seizure degree was reduced and the electroencephalograms were improved. The present study demonstrated that increased ICER and BDNF might be associated with the development of drug-resistance. The effect of Hip-LFS in the treatment of drug-resistant epileptic rats might be associated with increasing the levels of the ICER and the BDNF.