早期生长反应因子3基因转染精神分裂大鼠易感脑区的多模态磁共振成像研究

精神分裂症发病机制极其复杂，早期生长反应因子3(EGR3)是与精神分裂症发生密切相关的重要易感基因，然而该基因致精神分裂症具体机制仍不明确。本项目组前期采用磁共振波谱（1H-MRS）和功能磁共振成像（fMRI）技术，发现 EGR3基因异常表达引起精神分裂症大鼠易感脑区（前额叶、海马和丘脑）代谢改变和激活异常，提出前额叶-海马-丘脑环路障碍假说。本课题拟采取基因克隆技术将 EGR3基因转染大鼠海马建立精神分裂症模型，运用1H-MRS和定向代谢组学、静息态fMRI及弥散张量和纤维束追踪成像技术，对模型易感脑区从脑代谢、脑功能连接和脑结构连接三个方面进行深入系统研究，旨在从遗传神经影像学角度揭示精神分裂症脑代谢、脑功能和脑连接异常机理，发现早期诊断疾病的影像标志物。项目的实施将有助于阐明EGR3基因致精神分裂症脑异常发病机制，为精神分裂症临床早期诊断提供影像学证据和科学依据。

Schizophrenia is one of the most common mental disorders and the major causes of disability. The early growth response 3 (EGR-3) is an important susceptible gene associated with schizophrenia. However, so far, the etiology and pathological mechanisms of schizophrenia has not been fully elucidated. Our previous studies using hydrogen magnetic resonance spectroscopy (1H-MRS) and functional magnetic resonance imaging (fMRI) revealed that the abnormal expression of EGR-3 could induce the metabolic changes and dysfunctional activation in brain susceptible regions (prefrontal, hippocampus and thalamus). Therefore, we generate the hypothesis of prefrontal cortex - the hippocampus - the thalamus loop obstacle. The overall objective of this study is to investigate the mechanisms of abnormal brain function, metabolism and connection in schizophrenia through neuroimaging. We will first generate the transgenic rat model of schizophrenia by transfection of EGR3 gene lentiviral particles into the hippocampus of rats. The metabolism, function and fiber connection of susceptible brain regions will then be systematically studied using 1H-MRS, targeted metabolomics, resting state fMRI, diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT). In summary, the proposed study on EGR-3 induced schizophrenia-like rat model based on imaging genetics will elucidate the pathogenesis of schizophrenia and thus provide a scientific basis for the early diagnosis of schizophrenia using neuroimaging techniques.