荧光探针标记β淀粉样蛋白应用于氯胺酮所致认知功能障碍的机制研究

项目名称： 荧光探针标记β淀粉样蛋白应用于氯胺酮所致认知功能障碍的机制研究

项目编号： No.81460213

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李慧方洁

作者单位： 昆明医科大学

项目金额： 47万元

中文摘要： 娱乐性滥用氯胺酮等新型毒品对云南边疆地区的禁毒、戒毒工作产生了新的挑战，迫切需要建立新型毒品的神经机制研究方法。氯胺酮可导致滥用者精神依赖和认知功能障碍，β淀粉样蛋白被认为可能参与介导其中枢神经损害作用，但其作用机理尚不清楚。本项目模拟人类娱乐性滥用氯胺酮建立小鼠模型，即氯胺酮和乙醇两种不同给药模式，采用Morris 水迷宫实验、ELISA技术、免疫组化技术，评价不同给药模式下对小鼠脑部前额叶皮质和海马脑区中β淀粉样蛋白的介导作用。通过体外细胞标记、离体组织标记、在体组织标记等实验评估新型基于1,8萘啶BODIPY类荧光分子探针标记β淀粉样蛋白的生物学特性，选择最佳荧光分子探针标记β淀粉样蛋白，通过离体和在体标记实验观察其在神经细胞的形态和定位变化，研究其与氯胺酮滥用所致认知障碍的相关性，实现对其神经作用机制的可视化研究，这将为认识氯胺酮认知障碍的神经机制研究奠定基础和提供新的方法

中文关键词： BODIPY；分子探针；荧光标记；β；-淀粉样蛋白；“娱乐性滥用”氯胺酮；认知功能障碍

英文摘要： The situation that the new-type drugs, such as ketamine recreational abused, have been widespread in Yunnan province, especially in border area, have made drug control and drug treatment face the new challenge. The imperatives of many researchers is to establish the efficient method to research the neural mechanism of new-type drugs addiction. It is believed that β-amyloid mediated in phycological dependence and congnitive disorder following ketamine administration, but the mechanism remains unclear. In our this project, we mimic the model of human following ketamine recreational abused, that is, establishing the mice model of ketamine and ethanol abused under two different drug delivery systems. The evaluation of β-amyloid in prefrontal cortex and hippocampus mediated in cognition impairment following ketamine recreation abused in mice will be accomplished, through Morris water maze, ELISA, Immunohistochemistry. Also, the novel 1,8 naphthyridine-based BODIPY complex will be evaluated through binding to different forms of β-amyloid in vitro and vivo experiment. And imaging the β-amyloid will be realized through in vitro fluorescence staining of mice brain section, fluorescence immunohistochemical staining of brain tissue section, and vivo histology. The first example of visualized research β-amyloid in cognitive dysfunction under ketamine recreational abused in mice will be realized through neruo cell experiment, in vitro and in vivo fluorescence imaging for β-amyloid. This will lay the foundation of understand neural mechanism of ketamine abused and provide novel research methods.

英文关键词： BODIPY Molecular Probe;Fluorescence Imaging;β-Amyloid;Ketamine Recreational Abused;Cognitive Impairment