首页> 外文期刊>Nature >A role for glia in the progression of Rett's syndrome
【24h】

A role for glia in the progression of Rett's syndrome

机译:胶质细胞在瑞特综合征发展中的作用

获取原文
获取原文并翻译 | 示例
           

摘要

Rett's syndrome (RTT) is an X-chromosome-linked autism spectrum disorder caused by loss of function of the transcription factor methyi-CpG-binding protein 2 (MeCP2) Although MeCP2 is expressed in most tissues2, loss of MeCP2 expression results primarily in neurological symptoms~(1,3,4). Earlier studies suggested the idea that RTT is due exclusively to loss of MeCP2 function in neurons~(2,4,10). Although defective neurons clearly underlie the aberrant behaviours, we and others showed recently that the loss of MECP2 from glia negatively influences neurons in a non-cell-autonomous fashion~(11-13). Here we show that in globally MeCP2-defident mice, re-expression of Mecp2 preferentially in astrocytes significantly improved locomotion and anxiety levels, restored respiratory abnormalities to a normal pattern, and greatly prolonged lifespan compared to globally null mice. Furthermore, restoration of MeCP2 in the mutant astrocytes exerted a non-cell-autonomous positive effect on mutant neurons in vivo, restoring normal dendritic morphology and increasing levels of the excitatory glutamate transporter VGLUT1. Our study shows that glia, like neurons, are integral components of the neuropathology of RTT, and supports the targeting of glia as a strategy for improving the associated symptoms.
机译:Rett综合征(RTT)是一种X染色体连锁的自闭症谱系障碍,由转录因子methyi-CpG结合蛋白2(MeCP2)的功能丧失引起,尽管MeCP2在大多数组织中表达2,但MeCP2表达的丧失主要导致神经系统疾病症状〜(1,3,4)。较早的研究提出了这样的想法,即RTT完全是由于神经元MeCP2功能的丧失引起的(2,4,10)。尽管有缺陷的神经元显然是异常行为的基础,但我们和其他人最近表明,神经胶质细胞中MECP2的丧失以非细胞自主的方式对神经元产生了负面影响[11-13]。在这里,我们显示,在全局MeCP2缺陷小鼠中,优先在星形胶质细胞中重新表达Mecp2显着改善了运动和焦虑水平,将呼吸异常恢复为正常模式,并且与全局无效小鼠相比,寿命大大延长。此外,突变型星形胶质细胞中MeCP2的恢复在体内对突变型神经元发挥了非细胞自主的积极作用,恢复了正常的树突形态并增加了兴奋性谷氨酸转运蛋白VGLUT1的水平。我们的研究表明,神经胶质像神经元一样,是RTT神经病理学的组成部分,并且支持以神经胶质为目标作为改善相关症状的策略。

著录项

  • 来源
    《Nature》 |2011年第7357期|p.497-500|共4页
  • 作者单位

    Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA,Oregon Health and Science University, Portland, Oregon 97239, USA,Howard Hughes Medical Institute. Chevy Chase, Maryland 20815, USA;

    Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA,Oregon Health and Science University, Portland, Oregon 97239, USA,Howard Hughes Medical Institute. Chevy Chase, Maryland 20815, USA;

    Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA,Oregon Health and Science University, Portland, Oregon 97239, USA,Howard Hughes Medical Institute. Chevy Chase, Maryland 20815, USA;

    Oregon Health and Science University, Portland, Oregon 97239, USA,Departments of Behavioral Neuroscience and Neurology, Oregon Health and Science University, Portland, Oregon 97239, USA,Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon 97006, USA;

    Department of Pediatrics, The Ohio State University, Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio 43205, USA;

    Department of Pediatrics, The Ohio State University, Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio 43205, USA;

    Paul-Flechsig-lnstitute for Brain Research, Leipzig 04109, Germany;

    Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Gottingen,Germany,Institute of Physiology, University of Saarland, Homburg 37075, Germany;

    Oregon Health and Science University, Portland, Oregon 97239, USA,Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, Oregon 97202,USA,Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon 97202, USA;

    Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, New York 11794, USA;

    Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA,Oregon Health and Science University, Portland, Oregon 97239, USA,Howard Hughes Medical Institute. Chevy Chase, Maryland 20815, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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