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大鼠海马CA1区GABA能神经元在睡眠调节中的作用

The Role of GABAergic Neurons of Hippocampus CA1 Region in Sleep-Wake Cycle of Rats (Rattus norregicus)

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【作者】 张瑾李春华尹豆王烈成钟明奎赵乐章张景行汪凯

【Author】 ZHANG Jin①③ LI Chun-Hua② YIN Dou① WANG Lie-Cheng① ZHONG Ming-Kui① ZHAO Yue-Zhang① ZHANG Jing-Xing① WANG Kai③* (① Laboratory of Sleep Research,Anhui Medical University,Hefei 230032; ② Affiliated Hospital of Nanjing Command, Nanjing 210018; ③ Department of Neurology,Anhui Medical University,Hefei 230022,China)

【机构】 安徽医科大学睡眠障碍研究室安徽医科大学第一附属医院神经内科江苏省南京军区空军机关医院保健科

【摘要】 采用脑立体定位技术确定Sprague-Dawley大鼠(Rattus norregicus)双侧海马CA1区插管位置并进行核团埋管,同时安装脑电和肌电电极,用于记录大鼠皮层脑电活动和肌电活动。运用睡眠描记技术观察海马CA1区微量注射药物后对大鼠睡眠-觉醒周期的影响。发现海马内微量注射0.75μg、1.0μg的γ-氨基丁酸(GABA)后觉醒时间增加,分别为(120.7±13.3)min和(124.6±19.2)min(P<0.05),睡眠时间减少,分别为(119.4±13.3)min与(115.4±19.2)min(P<0.05),其中,深慢波睡眠时间(SWS2)分别减少53.3%(t=2.451,P<0.05)和63.5%(t=3.367,P<0.01);而微量注射1.0μgGABAA受体阻断剂荷包牡丹碱(Bic)后,睡眠时间增加(165.5±20.8)min(P<0.01),觉醒时间减少(74.5±20.8)min(P<0.01),其中,SWS2时间增加79.6%(t=2.600,P<0.05),并可对抗GABA的促醒效应;微量注射GABAB受体激动剂氯苯氨基丁酸(Bac)对睡眠-觉醒周期无直接影响,亦不能阻断GABA的促醒效应。结果提示,GABA在海马参与大鼠睡眠-觉醒周期的调节且具有促觉醒作用,GABA对睡眠的影响主要是通过改变深慢波睡眠成分实现的,GABAA受体参与介导了这一过程。

【Abstract】 Two stainless steel cannulae were implanted into Sprague-Dawley rat’s bilateral CA1 region of hippocampus by using brain stereotaxic technique. At the same time,four copper electrodes were screwed into the skull for electroencephalogram (EEG) recording and two silver wires in the neck muscle for electromyogram (EMG) recording. After drugs were microinjected into hippocampus,sleep-wake cycle was observed by polysomnography. After γ-amino-butyric acid (GABA,0. 75 μg,1. 0 μg) was microinjected into CA1 region of hippocampus,wake duration was enhanced (120. 7 ± 13. 3 min,124. 6 ± 19. 2 min,P < 0. 05),whereastotal sleep time was reduced (119. 4 ± 13. 3 min,115. 4 ± 19. 2 min,P < 0. 05) ,and deep slow wave sleep duration was also reduced by 53. 3% ( t = 2. 451,P < 0. 05) or 63. 5% ( t = 3. 367,P < 0. 01). In contrast, microinjection of bicuculline (Bic),a GAGAA receptor antagonist into hippocampus led to the opposite effects: total sleep time was increased (165. 5 ± 20. 8 min,P < 0. 01 ),wake duration was decreased (74. 5 ± 20. 8 min,P < 0. 01 ),and deep slow wave sleep duration was increased by 79. 6% ( t = 2. 600,P < 0. 05 ). Microinjection of baclofen (Bac),a GABAB receptor agonist,had no effect on sleep and could not block the effect of GABA either. These results indicate that GABA is involved in the regulation of sleep-wake cycle and promotes wake in the CA1 region of hippocampus. The effect of GABA on sleep is due to the change of deep slow wave sleep and GABAA receptor mediates the process.

【关键词】 海马γ-氨基丁酸睡眠觉醒
【Key words】 Hippocampusγ-amino-butyric acidSleepWakefulness
【基金】 安徽省高校优秀青年人才基金项目(No.2009SQRZ047);安徽省优秀青年科技基金项目(No.06043090)
  • 【文献出处】 动物学杂志 ,Chinese Journal of Zoology , 编辑部邮箱 ,2010年03期
  • 【分类号】R338.63
  • 【被引频次】20
  • 【下载频次】480
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