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癫痫敏感型沙鼠海马中上调的星形胶质细胞TWIK相关酸敏感钾通道1(TASK-1):抗癫痫药物的一个靶点。

Up-regulated astroglial TWIK-related acid-sensitive K+ channel-1 (TASK-1) in the hippocampus of seizure-sensitive gerbils: a target of anti-epileptic drugs.

作者信息

Kim Duk-Soo, Kim Ji-Eun, Kwak Sung-Eun, Choi Hui-Chul, Song Hong-Ki, Kimg Yeong-In, Choi Soo-Young, Kang Tae-Cheon

机构信息

Department of Anatomy, College of Medicine, Hallym University, Chunchon 200-702, South Korea.

出版信息

Brain Res. 2007 Dec 14;1185:346-58. doi: 10.1016/j.brainres.2007.09.043. Epub 2007 Sep 25.

Abstract

In order to identify the modulation of TASK (TWIK-related Acid-Sensitive K(+)) channel expressions in epilepsy, we conducted a comparative analysis of TASK channel immunoreactivities in the hippocampus of seizure-resistant (SR) and seizure-sensitive (SS) gerbils. There was no difference of the TASK-1 and TASK-2 channel expressions in the hippocampi of young SR and SS gerbils (1-2 months old). In adult SS gerbil hippocampus, TASK-1 immunoreactivity in astrocytes was higher than that in adult SR gerbil hippocampus. After seizures, TASK-1 immunoreactivity was significantly down-regulated in astrocytes of the SS gerbil hippocampus. In addition, various anti-epileptic drugs selectively affect TASK-1 immunoreactivity in astrocytes of the SS gerbil hippocampus. Gabapentin, lamotrigine, topiramate and valproic acid reduced the number of TASK-1(+) astrocytes in the hippocampus to 10-25% of that in saline-treated SS adult gerbils, whereas carbamazepine and vigabatrin decreased to approximately 50%. Therefore, the present study demonstrates that up-regulated TASK-1 immunoreactivity in astrocytes may be involved in the seizure activity of SS adult gerbils and suggests that the astroglial TASK-1 channel may be a target for epilepsy therapeutics.

摘要

为了确定癫痫中TASK(TWIK相关酸敏感钾离子通道)通道表达的调节情况,我们对癫痫抵抗(SR)和癫痫敏感(SS)沙鼠海马中的TASK通道免疫反应性进行了比较分析。在幼年SR和SS沙鼠(1 - 2个月大)的海马中,TASK - 1和TASK - 2通道表达没有差异。在成年SS沙鼠海马中,星形胶质细胞中的TASK - 1免疫反应性高于成年SR沙鼠海马。癫痫发作后,SS沙鼠海马星形胶质细胞中的TASK - 1免疫反应性显著下调。此外,各种抗癫痫药物选择性地影响SS沙鼠海马星形胶质细胞中的TASK - 1免疫反应性。加巴喷丁、拉莫三嗪、托吡酯和丙戊酸将海马中TASK - 1(+)星形胶质细胞的数量减少到生理盐水处理的成年SS沙鼠的10% - 25%,而卡马西平和氨己烯酸则减少到约50%。因此,本研究表明星形胶质细胞中上调的TASK - 1免疫反应性可能与成年SS沙鼠的癫痫发作活动有关,并提示星形胶质细胞TASK - 1通道可能是癫痫治疗的一个靶点。

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