调控少突胶质细胞细胞周期在精神分裂症发病机制与治疗中的作用研究

项目名称： 调控少突胶质细胞细胞周期在精神分裂症发病机制与治疗中的作用研究

项目编号： No.81473193

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杨红菊

作者单位： 中国人民解放军军事科学院军事医学研究院

项目金额： 65万元

中文摘要： 近年来研究发现精神分裂症病人存在少突胶质细胞发育异常、分化障碍等病理表现。调控少突胶质细胞分化成熟有望改善精神分裂症的认知障碍。我们前期工作发现损伤少突胶质细胞可诱发动物精神分裂样行为, 治疗药物喹硫平能改善动物的行为变化并促进少突胶质细胞分化。细胞周期控制细胞增殖与分化的精细平衡，我们认为少突胶质细胞细胞周期失调可能是导致精神分裂症病人少突胶质细胞分化异常的重要因素之一，而抗精神分裂药物可能是通过调控细胞周期来调控少突胶质细胞的增殖与分化。本课题拟采用激光显微捕捉技术探讨精神分裂症模型动物脑少突胶质细胞细胞周期调控因子的变化；确证抗精神分裂药物对少突胶质细胞细胞周期的作用；并探讨药理学与分子生物学手段干预细胞周期后少突胶质细胞的分化和精神分裂模型动物动物认知行为的变化。我们的研究结果对揭示精神分裂症的发生和抗精神分裂药物的作用机制以及探索精神分裂症的治疗具有极为重要的意义。

中文关键词： 精神分裂症；少突胶质细胞；抗精神病药物；细胞周期

英文摘要： Recent studies have shown oligodendrocyte abnormalities and differentiation deficits in brain of schizophrenia patients.Promoting of oligodendrocyte differentiation and maturity is beneficial for the treatment of cognitive sympotom of schizophrenia. In our previous studies, we found impairment of oligodendrocyte caused the schizophrenia like behavioral changes and antipsychotic drug quetiapine alleviated the schizophrenic behavioral changes and promote the differentiation of oligodendrocyte . Cell cycle regulation is crucial for the maintenance of cell populations and differentiation events. We hypothesis that cell cycle dysfunction of oligodendrocyte may be one of the important factor that contribute to the oligodendrocyte differentiation deficits shown in the schizophrenia patients, while antipsychotic drugs may control the growth and differentiation of oligodendrocyte by regulating the cell cycle proteins. This proposed studies will test the expression pattern of cell cycle genes of oligodendrocyte from the animals with schizophrenia symptom using Laser capture microdissection technique and investigate the effect of antipsychotics on the cell cycle of oligodendrocyte. We will test the effect of oligodendrocyte differentiation and animal cognitive behavior following the alteration of cell cycle through pharmacological and molecular biological interfereing.The completion of the proposed studies will provide a better understing of the pathophysiology of schizophrenia and the mechenism of the antipsychotic drugs . Our results will provide useful approaches for the treatment of cognitive disorder shown in schizophrenia patients.

英文关键词： schizophrenia;oligodendrocyte;antipsychotics;cell cycle