调控海马神经元中CDC42蛋白活性对小鼠记忆和焦虑行为影响的研究  

Effects of Modulation of CDC42 Activity in Hippocampal Neurons on Memory and Anxiety Behaviors of Mice

作　　者：邹超杰 唐义凯 杜书文 程宇琪 Chaojie ZOU;Yikai TANG;Shuwen DU;Yuqi CHENG(Dept.of Psychiatry,The 1st Affiliated Hospital of Kunming Medical University,Kunming Yunnan 650032;School of Life Sciences,McGovern Institute for Brain Research,Tsinghua University,Beijing 100084,China)

机构地区：[1]昆明医科大学第一附属医院精神科,云南昆明650032 [2]清华大学生命科学学院,清华大学麦戈文脑研究院,北京100084

出　　处：《昆明医科大学学报》2022年第11期1-8,共8页Journal of Kunming Medical University

基　　金：国家自然科学基金资助项目(82060259)。

摘　　要：目的建立动物模型研究海马神经元中细胞分裂周期蛋白42(Cell division cycle 42,CDC42)和认知缺陷之间的关系。方法包装携带CDC42突变体基因的腺病毒,通过显微注射操作使病毒感染健康小鼠海马脑区的兴奋性神经元,检测多种行为学范式下小鼠的认知表型。结果腺病毒能特异性的增强或降低CDC42蛋白在海马区兴奋性神经元的表达活性。CDC42蛋白活性的升高能促进小鼠24 h和96 h条件恐惧记忆的遗忘,同时能使小鼠表现出明显的焦虑行为。而抑制CDC42蛋白活性能促进条件恐惧记忆的维持。但是改变海马区CDC42蛋白活性不会影响小鼠的社交行为(P>0.05)。结论海马区CDC42蛋白活性的改变能够影响小鼠的条件恐惧记忆及焦虑行为,揭示了CDC42蛋白与认知缺陷表型有着密切的联系。这一调控模型可能为精神分裂症等相关精神疾病研究模型的建立提供新的方法和思路,而CDC42有望成为治疗精神疾病记忆损伤或焦虑的一个新的分子靶点。Objective To establish an animal model to investigate the relationship between cell division cycle 42(CDC42) and cognitive deficits in hippocampal neurons. Methods Adenovirus with CDC42 mutant gene was packaged to infect excitatory neurons in the hippocampus of healthy mice by microinjection. The cognitive phenotypes of mice under various behavioral patterns were detected. Results Adenovirus specifically enhanced or decreased the expression activity of CDC42 protein in excitatory neurons in the hippocampus. After the inhibition of CDC42 protein in the hippocampus,the conditioned memory of the mice decreased,significantly at 24 hours and 96hours,and enhancing CDC42 activity in the hippocampus made mice show an obvious anxiety behavior. However,neither enhancement nor inhibition of the CDC42 activity in the hippocampus had a significant effect on social behavior(P > 0.05). Conclusions The mice with altered CDC42 activity in hippocampal excitatory neurons may present a fear conditioning memory defect and significant anxiety behavior, this may suggest the relationship between cytoskeletal protein CDC42 and cognitive phenotypes. This regulatory model may provide new methods and ideas for the establishment of research models for mental disorders such as SZ and CDC42 is expected to become a new molecular target for the treatment of memory impairment or anxiety.

关 键 词：CDC42 精神分裂症 记忆损伤 焦虑 

分 类 号：R749.3[医药卫生—神经病学与精神病学]