不同强度运动改善PTSD小鼠恐惧记忆泛化及促海马神经再生效应研究  

Different exercise intensity alleviates fear memory generalization in PTSD mice by promoting adiponectin mediated adult hippocampal neurogene⁃sis

作　　者：金硕 张晓晓 吉宸萱 孙丽娜[1,2] JIN Shuo;ZHANG Xiaoxiao;JI Chenxuan;SUN Lina(College of Physical Education and Sports,Beijing Normal University,Beijing 100875,China;State Key Laboratory of Cognitive Neuroscience and Learning,Beijing Normal University,Beijing 100875,China)

机构地区：[1]北京师范大学体育与运动学院,北京100875 [2]北京师范大学认知神经科学与学习国家重点实验室,北京100875

出　　处：《中国病理生理杂志》2024年第6期1017-1024,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.32000835);北京师范大学认知神经科学与学习国家重点实验室开放课题(No.CNLZD2104)。

摘　　要：目的:探讨不同强度运动缓解创伤后应激障碍(PTSD)恐惧记忆泛化的作用及促海马神经再生中枢调控机制。方法:采用随机数字法将雄性C57 BL/6J小鼠分为对照(control)组、PTSD建模(PTSD)组、建模后高强度运动(PTSD-High)组和建模后低强度运动(PTSD-Low)组。采用条件性足部电击(CF)和单次-持续应激(SPS)相结合的方法,构建PTSD复合应激模型。利用条件性恐惧实验测试小鼠对恐惧记忆相似情境的辨别能力,评估小鼠恐惧记忆泛化程度,通过免疫荧光双标实验观察并量化小鼠海马DG区新生的未成熟神经元,使用ELISA测定血清脂联素的分泌水平。结果:(1)在条件性恐惧实验三个类似情境中,control组与PTSD-High组的不动时间均明显低于PTSD组。(2)免疫荧光双标染色图片显示,PTSD组小鼠海马DG区的新生神经元与未成熟神经元荧光信号降低,新生未成熟神经元纤维短而少。统计表明,与PTSD组相比,control、PTSD-High和PTSD-Low组小鼠新生未成熟神经元的细胞密度和树突分支点及长度均明显升高。(3)ELISA结果显示,control和PTSD-High组小鼠血清中脂联素水平均明显高于PTSD组和PTSD-Low组。结论:PTSD小鼠恐惧记忆泛化与海马神经再生水平下降有关。运动可能通过促进脂联素的分泌、促进海马神经再生改善恐惧记忆泛化。不同强度运动对比发现高强度运动改善效果更好。AIM:To explore the intensity-dependent effects of exercises to alleviate fear memory generalization in post-traumatic stress disorder(PTSD)and the underlying mechanism.METHODS:Male C57 BL/6J mice were randomly divided into the control group,PTSD group,high-intensity exercise(PTSD-High)group,and low-intensity exercise(PTSD-Low)group.PTSD model were created via using a combination of conditioned foot shock(CF)and single-prolonged stress(SPS).The contextual fear test was used to test the mice's ability to discriminate safety situations from fear condition.Immunofluorescence observed and quantified the newborn immature neurons in the DG area of the mice's hippocampus.ELISA was used to determine the secretion level of serum tissue adiponectin.RESULTS:(1)The immobility times for the PTSD-High and Control groups were significantly lower than those of the PTSD group.(2)Immunofluorescence analysis showed that the cell density,dendritic branching points and length of newborn immature neurons were elevated in High and Low groups compared to the PTSD group.(3)Adiponectin levels in the serum of the control and PTSD-High group were significantly higher than those in the PTSD group and PTSD-Low group.CONCLUSION:Fear memory establishment in PTSD mice is associated with decreased hippocampal neurogenesis.High-intensity exercise ameliorated fear memory by enhancing adiponectin secretion and promoting hippocampal neurogenesis.High-intensity exercise exerted better improvement of brain functions to PTSD model.

关 键 词：运动强度 脂联素 海马神经再生 创伤后应激障碍 恐惧记忆泛化 

分 类 号：R395.4[哲学宗教—心理学] R455[医药卫生—医学心理学] R749[医药卫生—基础医学]