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）：成年脊椎动物大脑可塑性相当普遍，对于理解神经退行性疾病以及中枢神经系统损伤的逆转极其重要，但其控制尚不清楚。现在已知小RNA是一种转录后调节机制，其作用过程迅速，与大脑的快速变化相一致。最近的研究表明小 RNA 在神经元发育和分化中发挥作用。研究还表明，从鱼类到哺乳动物，这些 RNA 的作用都是保守的。在这里，我们提出了一系列实验，使用独特的硬骨鱼模型系统，该系统具有特征明确的可塑且受社会控制的神经元变化。我们将使用该系统来评估小 RNA 在体内神经可塑性中的作用。在这个物种中，当雄性社会地位提升时，含有促性腺激素释放激素（GnRH1）的神经元体积会增加八倍，树突分支也会增加。这些形态变化发生在社会地位上升后的 3-5 天内，当动物社会地位下降时，这些形态变化会逆转。通过实验操纵社会地位的能力将使我们能够评估小RNA在体内调节成人大脑可塑性中的作用。我们将首先识别与鱼类经历社会上升、社会下降和无地位变化的不同阶段相关的小RNA。然后，我们将通过实验操纵目标小 RNA 的水平，以确定这些分子在调节大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，以绘制正在经历可塑性的大脑其他区域的图谱。这项工作将揭示小 RNA 是否以及哪些小 RNA 参与调节神经元可塑性。由于 GnRH1 系统在脊椎动物中是保守的，因此这项工作的结果将与所有脊椎动物相关。公共健康相关性：我们将鉴定小 RNA 并确定它们在调节体内神经元可塑性变化中的作用。了解这些小 RNA 是否以及如何在脊椎动物大脑中发挥作用，对于理解大脑在健康和疾病方面的变化如何受到调节具有广泛的应用。