ISSN 0439-755X
CN 11-1911/B
主办：中国心理学会
　　　中国科学院心理研究所
出版：科学出版社

心理学报 ›› 2011, Vol. 43 ›› Issue (05): 544-552.

• • 上一篇    下一篇

条件性恐惧大鼠边缘下区Cdk5激酶活性、caspase-3表达以及突触结构的变化

李培培;张丽丽;韦美;李敏   

  1. (1 第三军医大学护理系心理学教研室, 重庆 400038) (2 湖北医药学院药护学院, 湖北十堰 442000)
  • 收稿日期:2010-05-07 修回日期:1900-01-01 出版日期:2011-05-30 发布日期:2011-05-30
  • 通讯作者: 李敏

Cdk5 Kinase Activity, Caspase-3 Expression and Synaptic Structural Plasticity in Infra-limbic Cortex of Rats with Conditioned Fear

LI Pei-Pei;ZHANG Li-Li;WEI Mei;LI Min   

  1. (1 Department of Psychology, School of Nursing, the Third Military Medical University, Chongqing 400038, China)
    (2 Institute of Medicine and Nursing, Hubei University of Medicine, Shiyan 442000, China)
  • Received:2010-05-07 Revised:1900-01-01 Published:2011-05-30 Online:2011-05-30
  • Contact: LI Min

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摘要： 探讨条件性恐惧大鼠内侧前额叶皮层边缘下区(IL区)Cdk5激酶活性、凋亡因子caspase-3表达和突触结构的变化。采用声音结合足底电击的方法对大鼠建立条件性恐惧模型后, 在不同时间点测定IL区Cdk5激活剂P35和P25的蛋白表达水平、Cdk5激酶活性、caspase-3的阳性细胞数, 并观察突触结构的变化。结果发现, 大鼠在条件性恐惧建立后第2、4和8天, IL区的P25蛋白表达和Cdk5激酶活性均明显高于正常; caspase-3的免疫反应阳性细胞数在3个时间点也均多于正常; 透射电镜下观察到：在恐惧建立后的第8天, IL区突触的突触后致密物质(PSD)厚度变薄, 在恐惧建立后第22天突触数密度减少、PSD厚度仍小于正常。推测条件性恐惧的建立, 使大鼠IL区的P25水平和Cdk5活性高于正常, 引起IL区的突触结构发生改变, 导致大鼠的恐惧反应持续存在。

关键词: 条件性恐惧, 边缘下区, 细胞周期素依赖性蛋白激酶5, 突触结构

Abstract: Classical fear conditioning is a behavioral paradigm that is widely used to study the neuronal mechanisms of post-traumatic stress disorder. Previous studies have clearly identified the medial prefrontal cortex as a key brain area for fear memory traces, but the molecules involving are poorly understood. Recently, the neuronal cyclin dependent kinase 5 (Cdk5) has been implicated in both functional and structural plasticity through affecting ion channel conductance, dendritic spine formation, protein expressions and transcriptions in the postsynaptic neurons. Importantly, dysregulation of Cdk5 has been linked to cell apoptosis, which involves perturbation in synaptic function. How the kinase activity, expression of caspase-3 and synaptic structure have changed in infra-limbic cortex (IL) of conditioned fear? The present study is aimed to answer this question by two experiments.
Male adult SD rats were randomly divided into fear group and naive group. Conditioned fear model of rats was established by tone paired foot shock. At the 2nd, 4th and 8th days after fear conditioning, the Cdk5 activity, and expressions of P35 or P25 and caspase-3 in IL area were studied by immunoprecipitation and kinase assay, Western blotting and immunnohistochemical assay. Then the change of synaptic structure at the 8th and 22nd days after conditioned fear was observed with electron microscopy. The results of our experiment 1 showed that Cdk5 activity and expressions of P25 and caspase-3 were all higher in fear group than naive group. In experiment 2, the postsynaptic density (PSD) was thinner in fear group than naive group at the 8th and 22nd days after fear conditioning, but the numerical densities of IL synapse was decreased in fear group at the 22nd day after fear conditioning.
Our date suggested that at 8th days after conditioned fear established, the expression of P25 and Cdk5 activity in fear group were higher than naive group, which may lead to the change of synaptic structural plasticity of IL area and further lead to fear expression of rats.

Key words: conditioned fear, infra-limbic cortex, Cdk5, synaptic structure