AP3B型接合蛋白复合体μ亚基基因敲除小鼠痫性发作特征及其机制  

Mechanism of epileptic seizures in the neuron-specific adaptor protein complex type 3B knockout mice

作　　者：朱刚[1] 何志义[2] 时伟红[3] 陈晏[2] 孟祥亚[2] 邓淑敏[2] 

机构地区：[1]中国医科大学附属第一医院精神医学科,沈阳110001 [2]中国医科大学附属第一医院神经内科 [3]中国医科大学实验动物部

出　　处：《中华神经科杂志》2008年第2期114-117,共4页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目（30400146）

摘　　要：目的探讨AP3B型接合蛋白复合体斗亚基基因敲除小鼠（AP3M2KO小鼠）的痫性发作特征及机制。方法建立和繁殖AP3M2KO小鼠，利用远隔摄像和无线脑电图监测系统对小鼠的疴性发作表现及脑电图变化进行观测。利用脑内微小透析法对小鼠脑内神经递质的变化进行探讨。结果AP3M2KO小鼠在生后8周开始出现自发性痉挛症状。发作时小鼠脑颞叶脑电图出现典型的疴性波群。与野生小鼠相比，AP3M2KO小鼠海马神经细胞谷氨酸的基础及钾离子刺激性释放[分别为（0．35±0．08）pmol／20μl和（0．72±0．25）pmol／20μl]，γ-氨基丁酸（GABA）的基础释放[（2．94±1．69）fmol／20μl皆未见明显差异；GABA的钾离子刺激性释放[（63、5±11．8）fmol／20μl]明显减少（t=4．405，P〈0．05）。结论 AP3M2KO小鼠的痫性发作与人类癫痫发作的临床表现相类似，其痼性发作机制可能与GABA抑制性神经传递系统的功能低下有关。Objective To explore the mechanism of spontaneous seizures in adaptor protein complex type 3B knockout mice （AP3M2KO mice）. Methods AP3M2KO mice were generated. Seizures and electroencephalogram （EEG） were monitored using video camera and telemetry system. Glutamate and GABA releases were determined using in vivo microdialysis method. Results AP3M2KO mice began to suffer from spontaneous seizures 8 weeks after the birth, but did not show any other behavior abnormality. The onset of ictal discharge over the temporal region was synchronized with seizures. There were no significant differences in basal glutamate and GABA releases in hippocampus between AP3M2KO （ （0. 35 ±0. 08） pmol/20μl and （ 2. 94 ±1.69 ） fmol/20 μl respectively） and wild-type mice. However, the 50 mmol/L K^＋-evoked GABA release was impaired in AP3M2KO mice （（63.5 ± 11.8） fmol/20 μl vs （209. 2 ± 63.7 ） fmol/20 μl t= 4. 405, P 〈 0. 05 ）, whereas no significant difference was found in K ^＋ -evoked glutamate release. Conclusions AP3M2KO mice suffer from epileptic seizures similar to the clinical features of human epilepsy. The impairment of inhibitory GABAergic transmission is involved in the mechanism of spontaneous seizures in AP3M2KO mice.

关 键 词：癫痫 小鼠 基因敲除 衔接蛋白复合物3 衔接蛋白复合物β亚单位 衔接 蛋白复合物μ亚单位 

分 类 号：R686[医药卫生—骨科学]