低温低氧应激相关分子在大脑学习记忆功能损伤中的作用及其机制研究

项目名称： 低温低氧应激相关分子在大脑学习记忆功能损伤中的作用及其机制研究

项目编号： No.81330045

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 骆文静

作者单位： 中国人民解放军第四军医大学

项目金额： 290万元

中文摘要： 我国是高原面积广阔的国家，低温低氧造成的大脑认知脱适应性损伤是严重影响高原人群工作与生活的重大环境危害因素。以往研究发现，大脑空间认知能力在低温低氧环境中受损明显，但其机制并不清楚。课题组前期研究发现，低温低氧暴露可造成空间认知损伤并伴有海马可塑性改变，CIRP在低温低氧暴露中显著增强，CIRP-/-小鼠LTP幅度显著低于对照组，提示CIRP作为一种新发现的环境应激分子，在低温低氧应激空间认知损伤中发挥重要调节作用。基于前期研究，我们将以低温低氧对海马损伤的结构与分子影像学特点为切入点，深入研究低温低氧诱导的海马可塑性变化的机制，阐明环境应激分子CIRP在海马可塑性变化中的分子机理，探索CIRP在海马可塑性变化中的作用模式。为低温低氧环境大脑脱适应性损伤的治疗与预防提供实验基础和理论依据。

中文关键词： 高原低氧;低温;海马;空间认知;CIRP

英文摘要： There is large proportion of high altitude areas in our country. The cognitive impairment is often a form of maladaptation to chronic hypoxia and cold. The illness poses a great burden for the productivity and daily life of high-altitude dwellers. Previous studies found that the spatial memory is vulnerable to hypoxic and cold exposure without knowing underlying mechanisms. Our results showed that chronic hypoxic and cold exposure leads to functional and structural plasticity of hippocampus with concurrent impairment of spatial memory, and CIRP, a new stress-associated molecule, was increased after chronic hypoxic and cold exposure. We also found that CIRP-/- mice has lower amplitude of LTP than controls. The above results indicated that CIRP has an important role in the pathogenesis of environmental stress-induced cognitive impairment. Based on the previous studies, the current program aims to study the characteristics of molecular imaging of hypoxia and cold-induced changes of hippocampus, the molecular mechanism of chronic hypoxic and cold exposure-induced plasticity of hippocampus, and elucidate the role of CIRP, a new stress-associated molecule, in the plasticity of hippocampus. The current program will establish an experimental and theoretic base for the prevention and treatment of hypoxic and cold exposure-induced cognitive impairment.

英文关键词： high altitude hypoxia;cold;hippocampus;spatial memory;CIRP