BDNF相关microRNA的表达水平、基因型和精神分裂症病理症状、认知功能关系研究

项目名称： BDNF相关microRNA的表达水平、基因型和精神分裂症病理症状、认知功能关系研究

项目编号： No.81501160

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 吴兢勤

作者单位： 苏州大学

项目金额： 17.5万元

中文摘要： 脑源性神经营养因子(BDNF)和微小RNA(microRNA)在神经发育中起着重要作用，BDNF与miRNA之间还存在复杂相互作用，两者与精神分裂症病因及认知损伤紧密相关。目前我国尚缺乏BDNF相关miRNA的表达水平和基因型与精神分裂症发病机理、病症及认知损伤关系的系统研究。本课题将以中国汉族首次发作的精神分裂症患者和正常人为研究对象，通过ELISA、RT-PCR、SNP分析等分子生物技术，对比分析首发患者和对照人群中BDNF和BDNF相关miRNA的基因型、外周血单核细胞中BDNF和BDNF相关miRNA（miR-137, miR-132/miR-212，miR-134, miR-16/miR-195，miR-206，miR-30a-5p/miR-30e）表达水平，进而分析以上各因素及其交互作用与精神病理症状及认知功能的关联，为精神分裂症的临床诊断和新型药物治疗提供理论依据。

中文关键词： 精神分裂症；认知功能；脑源性神经营养因子；微小RNA；基因表达调控

英文摘要： Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a crucial role in neurodevelopment and neuroplasticity. MicroRNAs (miRNAs) are small non-coding RNAs of about 22-nucleotides in length that regulate gene expression at post-transcriptional level. Involved in neural development and function, both BDNF and miRNAs have been consistently implicated in pathophysiology of schizophrenia and its associated cognitive deficits. The regulatory networks between BDNF and miRNAs have also been observed. However, to date, there has not been a study focusing on a set of BDNF-related miRNAs in relation to psychopathology and cognitive dysfunction in schizophrenia. In this project, we will compare the expression levels of 9 BDNF-related miRNAs (miR-137, miR-132/miR-212，miR-134, miR-16/miR-195，miR-206，miR-30a-5p/miR-30e) in peripheral blood mononuclear cells by real time PCR between first-episode schizophrenia patients and healthy controls. These 9 miRNAs have been reported by at least 2 independent studies reporting its association with schizophrenia or cognitive function and interaction with BDNF. In parallel with miRNA expression, serum BDNF levels and 4 single nucleotide polymorphisms (SNPs) including BDNF Val66Met (rs6265) and 3 SNPs of miRNAs will also be examined. For the clinical data collection, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) will be used for cognitive performance in all subjects and Positive and Negative Syndrome Scale (PANSS) for the psychopathology of patients. The genotype and expression levels of BDNF and miRNAs will then be analysed in relation to syndrome and cognitive dysfunction in schizophrenia and the interplay between BDNF genotype/expression and miRNA genotype/expression will also be examined. This project will provide a comprehensive understanding of the pathogenesis of cognitive deficits in schizophrenia, which may have important clinical prospects for clinical biomarkers and novel treatments.

英文关键词： schizophrenia;cognition;BDNF;microRNA;regulation of gene expression