RNAi-Mediated Gene Suppression in Adult Mammalian CNS

RNAi介导的成年哺乳动物中枢神经系统基因抑制

• 批准号: 6668489
• 负责人: NEIL R SMALHEISER
• 金额: $ 15.59万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6668489
• 关键词: RNA; behavioral /social science research tag; behavioral genetics; brain cell; central nervous system; gene expression; genetic manipulation; genetic regulation; laboratory mouse; learning; mature animal; memory; messenger RNA; microarray technology; neurons; olfactory lobe; olfactory nerve; tissue /cell culture

DESCRIPTION: (provided by applicant) We hypothesize that RNA interference (RNAi) may occur under physiological conditions in the adult mammalian CNS, and that it may cause long-term suppression of specific genes. If RNAi does occur, it may be involved in adaptive, plastic neuronal responses such as underlie learning and drug addition. A program is proposed to test the putative role of RNAi in learning, which can be summarized as follows: First, subject mice to an olfactory learning paradigm. Second, identify genes that are suppressed during learning, particularly those linked experimentally to learning mechanisms. Third, prepare double-stranded RNAs for one or more of these identified mRNAs (siRNAs or sense-antisense hybrids) and introduce them into the brains of naive mice to elicit RNAi. Will learning be facilitated in these mice? Fourth, obtain biochemical evidence that RNAi is the endogenous mechanism responsible for suppressing the expression of a least some of these gene(s) during normal learning. In this R21 grant, to gain evidence needed as a preliminary to evaluate this hypothesis, we aim to: 1. Test whether gene suppression can be elicited experimentally in a sequence-specific manner within mammalian brain in vivo. 2. Test whether siRNA transfer can be an effective method for producing local gene suppression when injected within mammalian brain in vivo. These studies will pioneer the use of siRNA transfer as a potential means of selectivity knocking-down expression of neural genes, and will lay the foundation for testing the role of RNAi in learning and memory.

描述：（由申请人提供）

项目成果

The RNA-centred view of the synapse: non-coding RNAs and synaptic plasticity.

• DOI: 10.1098/rstb.2013.0504
• 发表时间: 2014-09-26
• 期刊: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
• 作者: Smalheiser NR

Preparing synaptoneurosomes from adult mouse forebrain.

从成年小鼠前脑制备突触神经体。

• DOI: 10.1007/978-1-62703-083-0_14
• 发表时间: 2013
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Lugli,Giovanni;Smalheiser,NeilR
• 通讯作者: Smalheiser,NeilR