Small RNA-mediated regulation of adult neuronal plasticity in vivo

小RNA介导的体内成人神经元可塑性调节

基本信息

批准号：
7996531
负责人：
RUSSELL D FERNALD
金额：
$ 15.84万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-04 至 2012-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7996531
关键词：
Adult African Aggressive behavior Animals Area Behavior Behavioral Biological Assay Biological Models Brain Brain region Cell Size Cells Cichlids Competence Cues Disease Fishes Future Gene Expression Profile Genes Genetic Transcription Gonadal structure Gonadotropin Hormone Releasing Hormone Gonadotropins Health Hypothalamic structure In Situ Hybridization Individual Length Life Mammals Maps Mediating Molecular Neurodegenerative Disorders Neuronal Plasticity Neurons Northern Blotting Outcome Peptides Phase Phenotype Physiological Pituitary Gland Plastics Preoptic Areas Principal Investigator Production Regulation Regulator Genes Role Series Signal Pathway Small RNA Social Change Social Controls Social Environment Social status Somatotropin System Techniques Testing Time Translating Untranslated RNA Vertebrates Work base central nervous system injury controlled release experience in vivo knock-down mRNA Expression male neuron development neuronal cell body novel overexpression pituitary gonadal axis programs public health relevance receptor reproductive research study response social steroid hormone teleost fish

项目摘要

DESCRIPTION (provided by applicant): Adult vertebrate brain plasticity is fairly widespread and extremely important in understanding neurodegenerative disease as well as reversal of central nervous system injuries yet its control is not well understood. Small RNAs are now known to be a post-transcriptional mechanism of regulation with a rapid course of action, consonant with rapid brain changes. Recent studies have shown a role for small RNAs in neuron development and differentiation. It has also been shown that the action of these RNAs is conserved from fish to mammals. Here we propose a series of experiments using a unique teleost fish model system with well-characterized neuronal changes that are plastic and under social control. We will use this system to assess the role(s) of small RNAs in neural plasticity in vivo. In this species, when a male ascends in social status, the gonadotropin releasing hormone (GnRH1) containing neurons increase eightfold in volume and increase their dendritic branching. These morphological changes occur within 3-5 days of social ascent and are reversed when the animal descends in social status. The ability to manipulate social status experimentally will allow us to assess the role of small RNAs in mediating adult brain plasticity in vivo. We will first identify small RNAs associated with distinct phases of fish undergoing social ascent, social descent and no status change. We will then experimentally manipulate levels of the targeted small RNAs to identify the causal role of these molecules in regulating plasticity in brain neurons. Molecules regulating plasticity in GnRH1 neurons can then be tested to map other regions of the brain undergoing plasticity. This work will reveal whether and which small RNAs participate in regulating neuronal plasticity. Since the GnRH1 system is conserved across vertebrates, the results from this work will be relevant for all vertebrates. PUBLIC HEALTH RELEVANCE: We will identify small RNAs and determine their role in regulating plastic changes of neurons in vivo. Understanding whether and how these small RNA act in the vertebrate brain will have wide reaching application in understanding how brain changes in health and disease are regulated.

描述（由申请人提供）：成年脊椎动物脑可塑性相当普遍，在理解神经退行性疾病以及中枢神经系统损伤的逆转方面非常重要，但其控制尚未得到充分了解。现在众所周知，小型RNA是调节后的转录机制，具有快速的作用，并随着大脑的快速变化而辅音。最近的研究表明，小RNA在神经元发育和分化中的作用。还已经表明，这些RNA的作用是从鱼到哺乳动物的。在这里，我们提出了一系列实验，使用独特的硬骨鱼类模型系统具有塑性和社会控制的特征性神经元变化。我们将使用该系统评估小RNA在体内神经可塑性中的作用。在该物种中，当男性登上社会地位时，促性腺激素释放激素（GNRH1）含有神经元的神经元增加了八倍，并增加了树突分支。这些形态学的变化发生在社会上升的3-5天内，当动物处于社会地位时会逆转。在实验上操纵社会地位的能力将使我们能够评估小RNA在体内介导成人脑可塑性中的作用。我们将首先确定与经历社会上升，社会下降和不变状态变化的鱼类不同阶段相关的小型RNA。然后，我们将通过实验操纵靶向小的RNA的水平，以确定这些分子在调节脑神经元可塑性中的因果作用。然后，可以测试调节GNRH1神经元可塑性的分子，以绘制脑的其他区域。这项工作将揭示以及哪些小RNA是否参与调节神经元可塑性。由于GNRH1系统在跨脊椎动物之间保存，因此这项工作的结果将与所有脊椎动物有关。公共卫生相关性：我们将确定小型RNA，并确定它们在调节体内神经元塑性变化中的作用。了解这些小RNA在脊椎动物大脑中的作用是否会在了解健康和疾病的大脑变化方面具有广泛的应用。