诱导性多能干细胞技术探索双相障碍发病机制的研究进展  

Progress on the pathogenesis of bipolar disorder based on induced pluripotent stem cells technology

作　　者：刘筱钰 袁爱花[1] 方贻儒[1] Liu Xiaoyu;Yuan Aihua;Fang Yiru(Clinical Research Center,Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200030,China)

机构地区：[1]上海交通大学医学院附属精神卫生中心,临床研究中心,200030

出　　处：《中华精神科杂志》2021年第5期390-395,共6页Chinese Journal of Psychiatry

基　　金：上海市市级科技重大专项(2018SHZDZX05);国家自然科学基金(81930033,81771465,81301146);国家重点研发计划“重大慢病重点专项”(2016YFC1307100);上海市西医引导类项目(18411961300)。

摘　　要：双相障碍目前已成为全球性的公共健康问题之一,由于缺乏准确可靠的研究手段,其发病机制尚未完全清楚。近年来,诱导性多能干细胞(induced pluripotent stem cells,iPSCs)技术已被用于双相障碍等精神疾病的发病机制探索,通过建立与双相障碍患者具有相同遗传信息的体外神经细胞模型,研究者们在神经发育、离子通道、线粒体功能、坍塌反应调节蛋白磷酰化、微小核糖核酸表达及免疫炎症反应等方面寻找到了双相障碍发病机制的线索。目前iPSCs技术尽管仍有诸多问题需要改善和解决,但因其可立足于临床样本,建立双相障碍神经细胞体外模型,因此具有巨大的基础研究及临床应用价值。期待基于iPSCs技术建立的双相障碍体外细胞模型能够早日突破各方面瓶颈,为精神疾病的病因研究和治疗带来曙光。Bipolar disorder(BD)has become one of the leading causes of healthy burdens globally,but the pathogenesis has not been fully understood due to the lacking of accurate and reliable research methods.Recently,the induced pluripotency stem cells(iPSCs)technology has been used to explore the mechanisms of psychiatric diseases,including bipolar disorder.Through the establishment of in vitro BD neuronal cell models with same genetic information as the patient donors,some pathogenic clues that were reported previously have been observed and validated.These clues are neurodevelopmental defects,ion channels dysfunctions,mitochondrial dysfunctions,abnormalities in phosphorylation of CRMP2,abnormal expressions of miRNA and dysfunctions of immune inflammatory procedures.Although a lot of problems and limitations need to be resolved and improved,iPSCs has great value in basic medicine researches and clinical applications because it can be based on clinical samples to establish the in vitro neuronal cell models of bipolar disorder.IPSC-derived in vitro BD models is expected to break through the bottleneck and eventually promote the pathological studies and new treatments in psychiatry.

关 键 词：双相情感障碍 诱导性多能干细胞 发病机制 

分 类 号：R749.4[医药卫生—神经病学与精神病学]