加味温胆汤对原代神经细胞及DISC1小鼠模型神经发育的干预作用研究

DISC1 Esv1属DISC1变异体，在精神类疾病的发病中具有关键作用，美国霍普金斯大学Dr.pletnikov研究发现，该基因对神经细胞的树突长度、突触分布等具有调节作用，有可能成为精神分裂症、抑郁症等精神病证的治疗新靶点。鉴于前国家基金项目对加味温胆汤修复神经元功能的发现，结合DISC1基因的研究成果，申请者提出工作假说：DISC1 Esv1剪切体可通过GSK-3β实现对神经细胞发育的调节，加味温胆汤有可能修复DISC1 Esv1剪切体对神经细胞的影响。为验证假说，实验将通过在体和离体实验，采用基因敲减、基因过表达等研究手段，结合荧光双标、激光共聚焦显微镜、电镜等研究方法，观察DISC1 Esv1剪切体在GSK-3β阻断和非阻断时，对神经细胞发育的损害，并通过中药复方加味温胆汤的干预处理，探讨中药复方对神经细胞发育异常的修复作用。研究结果将对开辟针对DISC1靶点新药研究具有重要意义

DISC1 Esv1 is a mutantion of DISC1 and it plays a key role in mental dieaseas. The Applicants uesed to co-work with Dr.pletnikov in johns hopkins and in their reaearches they founded that this gene can damage the neuronal development including the length of the dendrite and the number of the survive neurons. And from the Applicants' former reasearch in china, they founded that jiawei wendan decotion can ameliorate the neoronal development. So, base from the previous work and the prospect of the courrent work,we hypothesised that jiawen wendan decoction has the therapeutic effects of jiawei wendan decoction on abnormal neurodevelopment.We will study it in vitro and vivo , using the technology of gene knock down and overexpress, and applying the methods of immunstaining/ electron- microscope/laser-scanning-confocal-fluorescence-microscope. We will focus on the effect of DISC1 Esv1 on regulating neuronal development and the therapeutic effect of jiawei wendan decoction. The results will open up a new theopy for targeting DISC1 and it will enrich data for proving the efection of chinese medicine.