...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >BDNF modulates GABA_A receptors microtransplanted from the human epileptic brain to Xenopus oocytes
【24h】

BDNF modulates GABA_A receptors microtransplanted from the human epileptic brain to Xenopus oocytes

机译：BDNF调节从人类癫痫脑微移植到非洲爪蟾卵母细胞的GABA_A受体

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Cell membranes isolated from brain tissues, obtained surgically from six patients afflicted with drug-resistant temporal lobe epilepsy and from one nonepileptic patient afflicted with a cerebral oligodendroglioma, were injected into frog oocytes. By using this approach, the oocytes acquire human GABA_A receptors, and we have shown previously that the "epileptic receptors" (receptors transplanted from epileptic brains) display a marked run-down during repetitive applications of GABA. It was found that exposure to the neurotrophin BDNF increased the amplitude of the "GABA currents" (currents elicited by GABA) generated by the epileptic receptors and decreased their run-down; both events being blocked by K252A, a neurotrophin tyrosine kinase receptor B inhibitor. These effects of BDNF were not mimicked by nerve growth factor. In contrast, the GABAA receptors transplanted from the nonepileptic human hippocampal uncus (obtained during surgical resection as part of the nontumoral tissue from the oligodendroglioma margins) or receptors expressed by injecting rat recombinant α1β2γ2 GABA_A receptor subunit cDNAs generated GABA currents whose time-course and run-down were not altered by BDNF. Loading the oocytes with the Ca~(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetate-acetoxymethyl ester (BAPTA-AM), or treating them with Rp-8-Br-cAMP, an inhibitor of the cAMP-dependent PKA, did not alter the GABA currents. However, staurosporine (a broad spectrum PK inhibitor), bisin-dolylmaleimide I (a PKC inhibitor), and U73122 (a phospholipase C inhibitor) blocked the BDNF-induced effects on the epileptic GABA currents. Our results indicate that BDNF potentiates the epileptic GABAA currents and antagonizes their use-dependent run-down, thus strengthening GABAergic inhibition, probably by means of activation of tyrosine kinase receptor B receptors and of both PLC and PKC.
机译：从脑组织中分离出的细胞膜被注射到青蛙卵母细胞中，该细胞膜是通过手术从6例患有抗药性颞叶癫痫的患者和1例患有脑少突胶质细胞瘤的非癫痫患者中获得的。通过使用这种方法，卵母细胞获得了人的GABA_A受体，并且我们先前已经表明，“癫痫性受体”（从癫痫大脑移植的受体）在GABA的重复应用过程中显示出明显的衰弱。发现暴露于神经营养蛋白BDNF增加了由癫痫受体产生的“ GABA电流”（由GABA引发的电流）的幅度并减少了其衰弱。这两个事件均被神经营养蛋白酪氨酸激酶受体B抑制剂K252A阻断。神经生长因子不能模拟BDNF的这些作用。相比之下，从非癫痫性人类海马区（手术切除期间从少突胶质瘤边缘获得的非肿瘤组织的一部分）移植的GABA A受体或通过注射大鼠重组α1β2γ2GABA_A受体亚基cDNA表达的受体产生了GABA电流，其时程和运行-下来没有被BDNF改变。用Ca〜（2+）螯合剂1,2-双（2-氨基苯氧基）乙烷-N，N，N'，N'-四乙酸-乙酰氧基甲基酯（BAPTA-AM）加载卵母细胞，或用Rp-处理8-Br-cAMP是cAMP依赖性PKA的抑制剂，不会改变GABA电流。但是，星形孢菌素（一种广谱PK抑制剂），bisin-dolylmaleimide I（一种PKC抑制剂）和U73122（一种磷脂酶C抑制剂）阻断了BDNF诱导的对癫痫GABA电流的影响。我们的结果表明，BDNF增强了癫痫GABAA电流并拮抗其依赖于使用的消耗，从而可能通过激活酪氨酸激酶受体B受体以及PLC和PKC来增强GABA能抑制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号