成熟神经系统中活性依赖性的 microRNA 表达和功能-猫眼课题宝

成熟神经系统中活性依赖性的 microRNA 表达和功能

批准号：

8730236

负责人：

SOREN IMPEY

金额：

$37.76万

依托单位：

OHIO STATE UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

2010

资助国家：

美国

项目状态：

已结题

起止时间：

2010-09-15 至 2016-08-31

来源：

https://reporter.nih.gov/project-details/8730236

关键词：

Address Adult Affect Binding Sites Bioinformatics Biological Assay Brain CREB1 gene Cell Death Cell Survival Cells ChIP-seq Data Data Reporting Data Set Dendritic Spines Development Developmental Process Disease Down Syndrome Excision Functional RNA Genes Genetic Genetic Translation Goals Growth Health Hippocampus (Brain)Immunoprecipitation In Situ Hybridization Knock-out Knockout Mice Learning Maps Mediating Messenger RNA Methods MicroRNAs Morphogenesis Mouse Strains Mutant Strains Mice Nervous system structure Neuraxis Neuronal Plasticity Neurons Pathology Pathway interactions Pattern Physiological Play Process Proteins RNA Regulation Reporter Reporting Research Personnel Rett Syndrome Role Schizophrenia Seizures Series Small RNA Stimulus System Tamoxifen Testing Tetanus Helper Peptide Therapeutic Time Transgenic Organisms Validation Vertebral column Work axonal sprouting base comparative deep sequencing dentate gyrus design granule cell human DICER1 protein in vivo innovation insight loss of function mouse model nervous system disorder neuronal survival neuroprotection novel protein expression recombinase research study response screening small molecule synaptogenesis tool transcriptome sequencing

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DESCRIPTION (provided by applicant): MicroRNA is a recently characterized class of small, non-coding, RNA that repress mRNA translation. Work over the past several years has revealed important roles for microRNA in a vast array of developmental and disease-related processes. Within the developing mammalian central nervous system, results from dicer null mice support a role for microRNAs in neuronal morphogenesis and neuronal survival. However, relatively little is known about how neuronal activity regulates microRNA expression patterns in the mature nervous system and, importantly, whether microRNA regulate neuronal plasticity and cell viability. Based on recent work by a number of investigators, and on the preliminary data reported here, we propose that microRNA plays a key role in activity-dependent structural plasticity in the mature nervous system. To test this hypothesis we have assembled a novel set of genetically modified mouse models, and an array of genetic and functional screening assays. In Aim 1, we propose to utilize the Solexa deep sequence method to examine activity-dependent expression of non-coding RNA in the hippocampus. We will also examine the contribution of transcriptional networks that underlie activity-dependent neuronal plasticity and perform a series of experiments to identify functionally relevant microRNA targets. In Aim 2 we propose to determine the contribution of microRNA to adult neuronal structural plasticity and neuroprotection. To this end, we will employ an inducible form of Cre-recombinase to disrupt Dicer expression. The effects on both physiological and pathophysiological levels of neuronal activity will be examined. In Aim 3, we propose to determine the role of the microRNA-132 locus in activity-induced structural remodeling in vivo. A combination of knockout and tet-inducible microRNA mouse strains will be used to test this question. The data generated here should provide a wealth of new insights regarding how neuronal activity sculpts microRNA expression patterns, and, in turn, how these changes affect key aspects of neuronal plasticity and pathology.

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