MicroRNA-132 regulation of dendritic growth

MicroRNA-132对树突生长的调节

基本信息

批准号：
9033150
负责人：
RICHARD H. GOODMAN
金额：
$ 38.5万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9033150
关键词：
Adult Alleles Alzheimer&apos s Disease Autistic Disorder Behavior Behavior Control Biological Assay Biological Testing Brain Bromodeoxyuridine CREB1 gene Cell Culture Techniques Cell Cycle Cells EGF gene Exercise Exposure to Genetic Growth Heparin Binding Hippocampus (Brain)Individual Investigation Knock-out Knockout Mice Laboratories Learning Link LoxP-flanked allele Measures Mediating Mental Retardation Methods MicroRNAs Modeling Monitor Morphology Mouse Strains Mus Neurologic Neuronal Plasticity Neurons Newborn Infant Parkinson Disease Population Process Property Regulation Reporter Retroviral Vector Role Schizophrenia Series Signal Transduction Synapses System Testing Transgenes Viral adult neurogenesis base conditioned fear in vivo in vivo Model inhibitor/antagonist mRNA Expression neuronal growth neuronal survival newborn neuron novel strategies object recognition ratiometric relating to nervous system research study response sensor tissue culture

项目摘要

DESCRIPTION (provided by applicant): MicroRNAs contribute to critical brain functions and participate in multiple neurological and psychiatric conditions. Exactly how specific microRNAs relate to these processes remains unclear, however, for several reasons. First, genetic knockouts of brain-specific microRNAs have been difficult to generate. Second, predicting microRNA targets remains extraordinarily challenging. Third, methods for measuring microRNA levels in individual cells and, more importantly, linking these levels to the regulation of particuar targets are lacking. The overall objective of this application is to determine how the CREB-regulated microRNA, miR-132, directs dendritic growth and plasticity. Our specific aims are to: 1) Characterize the role of miR-132 in brain using a conditional knockout. We have already generated a mouse strain containing a floxed miR-132 allele and have shown, using a Cre-expressing retroviral vector, that newborn hippocampal neurons lacking miR-132 display a dramatic decrease in dendritic growth and branching. This was the first example of a neural-specific microRNA knockout, and we will use these mice to examine the role of miR-132 in adult neurogenesis, dendritic growth, and behaviors associated with activity-induced morphological changes, such as spatial learning and fear conditioning. 2) Determine whether heparin-binding (Hb)-EGF and the CDK inhibitor, p21, two miR-132 targets identified in Ago2-immunopurification assays, contribute to miR-132 effects on neuronal survival, morphology, and function. 3) Determine how changes in microRNA expression in individual neurons correlates with expression of specific microRNA targets. Assays of microRNA function typically average responses of large populations of cells. Using a new ratiometric microRNA sensor developed in our laboratory, we observed that individual neurons display large differences in the expression of miR-132. We will now ask whether these differences in miR-132 levels are associated with differences in target mRNA expression using, initially, cultured neurons and, subsequently, in vivo models.

描述（由申请人提供）：MicroRNA 有助于关键的大脑功能并参与多种神经和精神疾病。然而，由于多种原因，具体的 microRNA 与这些过程的具体关系仍不清楚。首先，大脑特异性 microRNA 的基因敲除很难产生。其次，预测 microRNA 靶点仍然极具挑战性。第三，缺乏测量单个细胞中 microRNA 水平的方法，更重要的是，缺乏将这些水平与特定靶点的调节联系起来的方法。本申请的总体目标是确定 CREB 调节的 microRNA（miR-132）如何指导树突生长和可塑性。我们的具体目标是：1) 使用条件敲除来表征 miR-132 在大脑中的作用。我们已经培育出含有 floxed miR-132 等位基因的小鼠品系，并使用表达 Cre 的逆转录病毒载体证明，缺乏 miR-132 的新生海马神经元的树突生长和分支显着减少。这是神经特异性 microRNA 敲除的第一个例子，我们将使用这些小鼠来研究 miR-132 在成年神经发生、树突生长以及与活动诱导的形态变化相关的行为（例如空间学习和恐惧）中的作用调理。 2) 确定肝素结合 (Hb)-EGF 和 CDK 抑制剂 p21（Ago2 免疫纯化测定中鉴定的两个 miR-132 靶标）是否有助于 miR-132 对神经元存活、形态和功能的影响。 3) 确定单个神经元中 microRNA 表达的变化如何与特定 microRNA 靶标的表达相关。 microRNA 功能的测定通常是大量细胞的平均反应。使用我们实验室开发的新型比例式 microRNA 传感器，我们观察到单个神经元的 miR-132 表达存在巨大差异。我们现在将首先使用培养神经元，随后使用体内模型来询问 miR-132 水平的这些差异是否与靶标 mRNA 表达的差异相关。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Capturing microRNA targets using an RNA-induced silencing complex (RISC)-trap approach.

使用 RNA 诱导沉默复合物 (RISC) 陷阱方法捕获 microRNA 靶标。

DOI：
发表时间：
2012-12-11
期刊：
影响因子：
11.1
作者：
Cambronne, Xiaolu A;Shen, Rongkun;Auer, Paul L;Goodman, Richard H
通讯作者：
Goodman, Richard H

Memory formation and retention are affected in adult miR-132/212 knockout mice.

成年 miR-132/212 敲除小鼠的记忆形成和保留受到影响。

DOI：
发表时间：
2015
期刊：
影响因子：
2.7
作者：
Hernandez;Smith, Pascal Y;Filali, Mohammed;Goupil, Claudia;Planel, Emmanuel;Magill, Stephen T;Goodman, Richard H;Hébert, Sébastien S
通讯作者：
Hébert, Sébastien S