...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >A 5-HT1D-receptor agonist protects Dravet syndrome mice from seizure and early death
【24h】

A 5-HT1D-receptor agonist protects Dravet syndrome mice from seizure and early death

机译：一个5-HT1D-受体激动剂保护癫痫和早期死亡的Dravet综合征小鼠

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

Mutations in the SCN1A gene encoding the Nav1.1 sodium channel cause several forms of epilepsy, the most severe is Dravet syndrome (DS). DS patients are at high risk for sudden death and seizures are often triggered by fever or hyperthermia. To improve understanding of how serotonergic ligands might influence DS in this study, we tested several drugs for their effect on hyperthermia-induced seizure using a mouse model of DS consisting of a heterozygous loss of function ofScn1A. We found that a mixed 5-HT(2A/2C)receptor agonist had no effect while a mixed 5-HT(1B/D)receptor agonist had a modest effect reducing the severity of seizures. Hypothesizing selective agonists may be more effective, we tested selective 5-HT(1B)and 5-HT(1D)receptor agonists, CP-93129 and GR-46611, respectively. Of these GR-46611 significantly increased the threshold of hyperthermia-induced seizure and lowered seizure severity. Given chronically at 1 mg kg(-1) day(-1), GR-46611 also significantly improved survival of DS mice. Thus, 5-HT1D-receptors may represent a meaningful target for pharmacotherapy for DS with potential relevance for related forms of epilepsy, particularly those with a known sensory trigger such as heat.
机译：编码Nav1的SCN1A基因突变。1钠通道导致多种形式的癫痫，最严重的是Dravet综合征（DS）。DS患者猝死的风险很高，癫痫发作通常由发热或高热引起。为了更好地理解5-羟色胺配体可能如何影响DS，在本研究中，我们使用一个由SCN1a杂合性功能丧失组成的DS小鼠模型，测试了几种药物对热疗诱导的癫痫发作的影响。我们发现混合5-HT（2A/2C）受体激动剂没有效果，而混合5-HT（1B/D）受体激动剂对降低癫痫发作的严重程度有一定的效果。假设选择性激动剂可能更有效，我们分别测试了选择性5-HT（1B）和5-HT（1D）受体激动剂CP-93129和GR-46611。其中GR-46611显著提高了高温诱发癫痫发作的阈值，降低了癫痫发作的严重程度。长期给予1 mg kg（-1）天（-1），GR-46611也显著提高了DS小鼠的存活率。因此，5-HT1D受体可能是DS药物治疗的一个有意义的靶点，可能与相关形式的癫痫有关，尤其是那些具有已知感觉触发因素（如热）的癫痫。

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