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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus
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microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus

机译：microRNA-132调节成年海马中新生神经元的树突状生长和乔化

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摘要

Newborn neurons in the dentate gyrus of the adult hippocampus rely upon Camp response element binding protein (CREB) signaling for their differentiation into mature granule cells and their integration into the dentate network. Among its many targets, the transcription factor CREB activates expression of a gene locus that produces two microRNAs, miR-132 and miR-212. In cultured cortical and hippocampal neurons, miR-132 functions downstream from CREB to mediate activity-dependent dendritic growth and spine formation in response to a variety of signaling pathways. To investigate whether miR-132 and/or miR-212 contribute to the maturation of dendrites in newborn neurons in the adult hippocampus, we inserted LoxP sites surrounding the miR-212/132 locus and specifically targeted its deletion by stereotactically injecting a retrovirus expressing Cre recombinase. Deletion of the miR-212/132 locus caused a dramatic decrease in dendrite length, arborization, and spine density. The miR-212/132 locus may express up to four distinct microRNAs, miR-132 and -212 and their reverse strands miR-132* and -212*. Using ratiometric microRNA sensors, we determined that miR-132 is the predominantly active product in hippocampal neurons. We conclude that miR-132 is required for normal dendrite maturation in newborn neurons in the adult hippocampus and suggest that this microRNA also may participate in other examples of CREB-mediated signaling.
机译：成年海马齿状回中的新生神经元依赖于Camp应答元件结合蛋白（CREB）信号转导成成熟的颗粒细胞并整合到齿状网络中。在其许多靶标中，转录因子CREB激活一个基因座的表达，该基因座产生两个microRNA，即miR-132和miR-212。在培养的皮质和海马神经元中，miR-132在CREB下游起作用，以响应各种信号传导途径介导活性依赖性树突状生长和脊柱形成。为了研究miR-132和/或miR-212是否有助于成人海马新生神经元中树突的成熟，我们在miR-212 / 132位点周围插入了LoxP位点，并通过立体定向注射表达Cre的逆转录病毒专门靶向其缺失重组酶。 miR-212 / 132基因座的删除导致枝晶长度，乔木化和书脊密度急剧下降。 miR-212 / 132位点可表达多达四个不同的microRNA，即miR-132和-212及其反向链miR-132 *和-212 *。使用比例式microRNA传感器，我们确定miR-132是海马神经元中的主要活性产物。我们得出的结论是，成年海马新生神经元中正常树突成熟需要miR-132，并且表明该microRNA也可能参与CREB介导的信号传导的其他例子。

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  • 作者

    Stephen T. Magill; Xiaolu A. Cambronne; Bryan W. Luikart; Daniel T. Lioy; Barbara H. Leighton; Gary L Westbrook; Gail Mandel; Richard H. Goodman;

  • 作者单位

    Vollum Institute Oregon Health and Science University, Portland, OR 97239;

    Vollum Institute Oregon Health and Science University, Portland, OR 97239;

    Vollum Institute Oregon Health and Science University, Portland, OR 97239;

    Vollum Institute Oregon Health and Science University, Portland, OR 97239,Howard Hughes Medical Institute, Oregon Health and Science University, Portland, OR 97239;

    Vollum Institute Oregon Health and Science University, Portland, OR 97239;

    Vollum Institute Oregon Health and Science University, Portland, OR 97239;

    Vollum Institute Oregon Health and Science University, Portland, OR 97239,Howard Hughes Medical Institute, Oregon Health and Science University, Portland, OR 97239;

    Vollum Institute Oregon Health and Science University, Portland, OR 97239;

  • 收录信息 美国《科学引文索引》(SCI);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

    microRNA-212; neurogenesis; plasticity; learning;

    机译：微小RNA-212;神经发生可塑性;学习;

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