...
  • 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 >Enhanced dense core granule function and adrenal hypersecretion in a mouse model of Rett syndrome.
【24h】

Enhanced dense core granule function and adrenal hypersecretion in a mouse model of Rett syndrome.

机译：Rett综合征小鼠模型中增强的致密核心颗粒功能和肾上腺分泌过多。

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

Rett syndrome (RTT) is a progressive developmental disorder resulting from loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2), a transcription regulatory protein. The RTT phenotype is complex and includes severe cardiorespiratory abnormalities, dysautonomia and behavioral symptoms of elevated stress. These findings have been attributed to an apparent hyperactivity of the sympathetic nervous system due to defects in brainstem development; however, the possibility that the peripheral sympathoadrenal axis itself is abnormal has not been explored. The present study demonstrates that the adrenal medulla and sympathetic ganglia of Mecp2 null mice exhibit markedly reduced catecholamine content compared with wild-type controls. Despite this, null animals exhibit significantly higher plasma epinephrine levels, suggesting enhanced secretory granule function in adrenal chromaffin cells. Indeed, we find that Mecp2 null chromaffin cells exhibit a cell autonomous hypersecretory phenotype characterized by significant increases in the speed and size of individual secretory granule fusion events in response to electrical stimulation. These findings appear to indicate accelerated formation and enhanced dilation of the secretory granule fusion pore, resulting in elevated catecholamine release. Our data therefore highlight abnormal catecholamine function in the sympathoadrenal axis as a potential source of autonomic dysfunction in RTT. These findings may help to explain the apparent 'overactivity' of the sympathetic nervous system reported in patients with RTT.
机译：Rett综合征（RTT）是一种进行性发育障碍，是由编码甲基CpG结合蛋白2（MeCP2）（一种转录调节蛋白）的基因中的功能丧失突变引起的。 RTT表型很复杂，包括严重的心肺异常，自主神经功能不全和压力升高的行为症状。这些发现归因于由于脑干发育缺陷引起的交感神经系统明显活动亢进。但是，尚未探讨周围交感肾上腺轴本身是否异常的可能性。本研究表明，与野生型对照相比，Mecp2缺失小鼠的肾上腺髓质和交感神经节的儿茶酚胺含量明显降低。尽管如此，没有动物的血浆肾上腺素水平明显升高，表明肾上腺嗜铬细胞中分泌颗粒的功能增强。实际上，我们发现Mecp2无效的嗜铬细胞表现出细胞自主性高分泌表型，其特征是响应电刺激，单个分泌颗粒融合事件的速度和大小显着增加。这些发现似乎表明分泌性颗粒融合孔的加速形成和增强的膨胀，导致儿茶酚胺的释放增加。因此，我们的数据强调了交感肾上腺轴儿茶酚胺功能异常，这可能是RTT自主神经功能障碍的潜在原因。这些发现可能有助于解释RTT患者中交感神经系统的明显“过度活动”。

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