DNA BASE MODIFICATIONS IN NEURAL PLASTICITY AND NEUROPSYCHIATRIC DISORDERS

神经可塑性和神经精神疾病中的 DNA 碱基修饰

• 批准号: 8799136
• 负责人: Timothy W Bredy
• 金额: $ 30.02万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8799136
• 关键词: 8-hydroxyguanosine; Adaptive Behaviors; Address; Adult; Anxiety Disorders; Area; Base Excision Repairs; Behavioral; Bioinformatics; Chromatin; Cognitive; Complementary DNA; DNA; DNA Double Strand Break; DNA Modification Process; DNA Repair Pathway; Development; Disease; Environment; Epigenetic Process; Eukaryota; Exposure to; Frequencies; Fright; Future; Gene Expression; Gene Expression Regulation; Gene Targeting; Genome; Genomic DNA; Genomics; Guanine; Heterogeneity; Knowledge; Learning; Light; Longevity; Memory; Mitotic; Modification; Molecular; Mutagens; Nature; Neurodegenerative Disorders; Neuronal Plasticity; Neurons; Oxidative Stress; Pattern; Population; Pre-Clinical Model; Process; Protocols documentation; Regulation; Research; Role; Stimulus; Technology; Testing; Therapeutic; Therapeutic Intervention; Tissues; Toxin; Work; age related; base; biological systems; bisulfite; carcinogenesis; cell type; experience; gel electrophoresis; gene function; innovation; insight; irradiation; neuropsychiatry; new technology; novel; oxidation; pressure; public health relevance; research study; response

DESCRIPTION (provided by applicant): Although epigenetic regulation of gene expression has been shown to be associated with experience- dependent neural plasticity and memory formation, due to technical and conceptual limitations, the full repertoire of DNA base modifications and their role in neuropsychiatric disease remains equivocal. In this project, new technology will be developed to more precisely identify activity-dependent epigenetic mechanisms in neuronal populations selectively activated by learning and challenge current concepts related to the full repertoire of DNA base modifications and their role in regulating gene expression. Specifically, we will determine whether there is a causal relationship between various DNA base modifications and rapid behavioral adaptation, and we will advance the state of knowledge regarding the molecular mechanisms underlying the memory in a preclinical model of fear-related anxiety disorder.

描述（由申请人提供）：尽管基因表达的表观遗传调节已显示与经验依赖性神经可塑性和记忆形成相关，但由于技术和概念上的限制，DNA碱基修饰的全部谱及其在神经精神疾病中的作用仍然不明确.在该项目中，将开发新技术，以更精确地识别通过学习选择性激活的神经元群体中的活性依赖性表观遗传机制，并挑战与DNA碱基修饰及其在调节基因表达中的作用相关的完整库的当前概念。具体来说，我们将确定各种DNA碱基修饰和快速行为适应之间是否存在因果关系，我们将推进关于恐惧相关焦虑症临床前模型中记忆的分子机制的知识状态。