...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neuron >Enhancement of inhibitory neurotransmission by GABAA receptors having α2,3-subunits ameliorates behavioral deficits in a mouse model of autism
【24h】

Enhancement of inhibitory neurotransmission by GABAA receptors having α2,3-subunits ameliorates behavioral deficits in a mouse model of autism

机译：具有α2,3-亚基的GABAA受体增强抑制性神经传递可改善自闭症小鼠模型的行为缺陷

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

Autism spectrum disorder (ASD) may arise from increased ratio of excitatory to inhibitory neurotransmission in the brain. Many pharmacological treatments have been tested in ASD, but only limited success has been achieved. Here we report that BTBR T+ Itpr3tf/J (BTBR) mice, a model of idiopathic autism, have reduced spontaneous GABAergic neurotransmission. Treatment with low nonsedatingonanxiolytic doses of benzodiazepines, which increase inhibitory neurotransmission through positive allosteric modulation of postsynaptic GABAA receptors, improved deficits in social interaction, repetitive behavior, and spatial learning. Moreover, negative allosteric modulation of GABAA receptors impaired social behavior in C57BL/6J and 129SvJ wild-type mice, suggesting that reduced inhibitory neurotransmission may contribute to social and cognitive deficits. The dramatic behavioral improvement after low-dose benzodiazepine treatment was subunit specific-the α2,3-subunit-selective positive allosteric modulator L-838,417 was effective, but the α1-subunit-selective drug zolpidem exacerbated social deficits. Impaired GABAergic neurotransmission may contribute to ASD, and α2,3-subunit-selective positive GABAA receptor modulation may be an effective treatment.
机译：自闭症谱系障碍（ASD）可能是由于大脑中兴奋性与抑制性神经传递的比率增加所致。在ASD中已经测试了许多药物治疗方法，但是仅取得了有限的成功。在这里我们报告BTBR T + Itpr3tf / J（BTBR）小鼠，特发性自闭症的模型，减少了自发的GABA能神经传递。低镇静/非抗焦虑剂量的苯二氮卓类药物的治疗，可通过对突触后GABAA受体的正向变构调节来增加抑制性神经传递，改善社交互动，重复性行为和空间学习方面的缺陷。此外，GABAA受体的负变构调节影响了C57BL / 6J和129SvJ野生型小鼠的社交行为，表明抑制性神经传递减少可能导致社交和认知缺陷。小剂量苯二氮卓类药物治疗后行为的显着改善是亚基特异性的-α2,3-亚基选择性正构构调节剂L-838,417有效，但α1亚基选择性药物唑吡坦加剧了社会缺陷。 GABA能神经传递受损可能有助于ASD，α2,3-亚基选择性GABAA受体阳性正调控可能是一种有效的治疗方法。

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