内侧前额叶皮层神经可塑性与条件恐惧模型小鼠恐惧记忆的相关性分析  

Correlation analysis of neuroplasticity in the medial prefrontal cortex and fear memory in fear conditioned model mice

作　　者：杜英杰 陈红芽 白亚璠 张悦 刘敏[1] 张丛雅 陈一萌 李赫 王古岩 李铭[1] Du Yingjie;Chen Hongya;Bai Yafan;Zhang Yue;Liu Min;Zhang Congya;Chen Yimeng;Li He;Wang Guyan;Li Ming(Department of Anesthesiology,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China)

机构地区：[1]首都医科大学附属北京同仁医院麻醉科,100730

出　　处：《北京医学》2024年第12期1026-1030,共5页Beijing Medical Journal

基　　金：国家自然科学基金(82270411);北京市医院管理局“登峰”计划(DFL20220203);首都卫生发展科研专项(首发2024-2-2058);首都医科大学附属北京同仁医院青年拔尖人才(2023-YJJ-ZZL-018)。

摘　　要：目的探讨内侧前额叶皮层(medial prefrontal cortex,mPFC)神经可塑性与条件恐惧(fear conditioning,FC)模型小鼠恐惧记忆的相关性,为创伤后应激障碍(post-traumatic stress disorder,PTSD)的预防和治疗提供新的策略。方法选取12周龄雄性C57BL/6J小鼠24只,随机分为FC(-)组和FC(+)组,每组12只,分别接受非FC和FC流程。通过FC和恐惧消退范式建立PTSD动物模型,以僵住时间百分比代表恐惧记忆。采用高尔基染色和蛋白质免疫印迹实验技术分析mPFC神经可塑性的变化。结果与FC(-)组相比,FC(+)组小鼠在FC造模后[(34.08±15.37)%比(0.67±1.61)%]、恐惧消退训练时[(43.42±20.87)%比(6.75±4.61)%]、恐惧消退测试时[(31.75±16.59)%比(9.58±5.78)%]、声音线索恐惧测试时[(14.00±5.12)%比(7.33±4.50)%]、场景线索恐惧测试时[(22.50±15.31)%比(2.75±3.02)%]的僵住时间百分比更高;mPFC区域树突分支总数和树突棘密度更低[(44.67±9.20)比(58.08±15.08),(6.26±1.98)比(8.81±2.25)];mPFC脑区脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)[(0.62±0.20)比(1.00±0.15)]、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)[(0.60±0.16)比(1.00±0.13)]和突触后密度蛋白95(postsynaptic density protein 95,PSD95)[(0.85±0.09)比(1.00±0.03)]表达水平更低,差异均有统计学意义(P<0.05)。结论mPFC脑区神经可塑性的降低可能与恐惧记忆的增强有关,增强mPFC区域的神经可塑性可能有助于促进恐惧记忆的消退,为PTSD的治疗提供了新的潜在靶点。Objective To explore the correlation between neuroplasticity of the medial prefrontal cortex(mPFC)and fear memory in fear conditioned(FC)model mice,and to provide new strategies for the prevention and treatment of posttraumatic stress disorder(PTSD).Methods A total of 24 male C57BL/6J mice aged 12 weeks were selected,and were randomly divided into FC(-)group and FC(+)groups,with 12 mice in each group,receiving non-FC and FC procedures,respectively.PTSD mice models were established through FC and fear extinction paradigms,and the percentage of freezing time was used to represent fear memory.The changes in neuroplasticity in the mPFC was analyzed by Golgi staining and western blotting experiments.Results Compared with the FC(-)group,the mice in the FC(+)group had higher percentages of freezing time after FC[(34.08±15.37)%vs.(0.67±1.61)%],during fear extinction training[(43.42±20.87)%vs.(6.75±4.61)%],during fear extinction testing[(31.75±16.59)%vs.(9.58±5.78)%],during auditory cue fear testing[(14.00±5.12)%vs.(7.33±4.50)%],and during contextual cue fear testing[(22.50±15.31)%vs.(2.75±3.02)%].The total number of dendritic branches and the density of dendritic spines in the mPFC region were lower[(44.67±9.20)vs.(58.08±15.08),(6.26±1.98)vs.(8.81±2.25)].The expression levels of brain-derived neurotrophic factor(BDNF)[(0.62±0.20)vs.(1.00±0.15)],mammalian target of rapamycin(mTOR)[(0.60±0.16)vs.(1.00±0.13)],and postsynaptic density protein 95(PSD95)[(0.85±0.09)vs.(1.00±0.03)]in the mPFC brain region were lower,and the differences were statistically significant(P<0.05).Conclusions The reduction of neuroplasticity in the mPFC region may be related to the enhancement of fear memory.Enhancing neuroplasticity in the mPFC region may help promote the extinction of fear memory,and providing a new potential target for the treatment of PTSD.

关 键 词：内侧前额叶皮层 神经可塑性 条件恐惧 恐惧记忆 创伤后应激障碍 

分 类 号：R74[医药卫生—神经病学与精神病学]