中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (12): 1956-1961.doi: 10.4103/1673-5374.197137

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

亚睡眠剂量异丙酚损害海马神经元对空间记忆的提取

  

  • 收稿日期:2016-11-22 出版日期:2016-12-31 发布日期:2016-12-31
  • 基金资助:
    中国国家自然科学基金项目(81571039);安徽医科大学第一附属医院国家自然科学基金培育基金项目(2015KJ12)

Subhypnotic doses of propofol impair spatial memory retrieval in rats

Hu Liu, Ting Wang, Wei Dai, Zheng Jiang, Yuan-hai Li, Xue-sheng Liu*   

  1. First Afliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
  • Received:2016-11-22 Online:2016-12-31 Published:2016-12-31
  • Contact: Xue-sheng Liu, Ph.D., liu711029@hotmail.com.
  • Supported by:
    This work was fnancially supported by the National Natural Science Foundation of China, No. 81571039; the Foundation for Fostering the National Natural Science Foundation of First Afliated Hospital of Anhui Medical University in China, No. 2015KJ12.

摘要:

大量研究结果显示异丙酚对记忆过程有着深刻的影响,最近的一项研究认为海马糖原合成酶激酶3β能参与记忆提取过程。为验证此学说,实验对成年SD大鼠进行多次Morris水迷宫任务训练,然后观察亚睡眠剂量异丙酚对水迷宫探索实验时在目的象限停留的时间,即记忆提取测试结果的影响。结果显示,检测前5min腹腔注射25 mg/kg异丙酚能显著减少大鼠在目标象限活动时间比例,但不影响其自发活动,即仅影响记忆提取。记忆提取伴随着糖原合成酶激酶3β丝氨酸9残基的磷酸化降低,而酪氨酸216残基磷酸化与此无关。异丙酚能阻断糖原合成酶激酶3β丝氨酸9残基的磷酸化。表明亚催眠剂量异丙酚能通过影响糖原合成酶激酶3β信号,影响记忆提取,参与遗忘过程。 

orcid: 0000-0003-4324-282X (Xue-sheng Liu)

关键词: 神经再生, 糖原合成酶激酶3β, 丙泊酚, 记忆提取, Morris水迷宫

Abstract: Abundant evidence indicates that propofol profoundly affects memory processes, although its specifc effects on memory retrieval have not been clarifed. A recent study has indicated that hippocampal glycogen synthase kinase-3β (GSK-3β) activity affects memory. Constitutively active GSK-3β is required for memory retrieval, and propofol has been shown to inhibit GSK-3β. Tus, the present study examined whether propofol affects memory retrieval, and, if so, whether that effect is mediated through altered GSK-3β activity. Adult Sprague-Dawley rats were trained on a Morris water maze task (eight acquisition trials in one session) and subjected under the in?uence of a subhypnotic dose of propofol to a 24-hour probe trial memory retrieval test. Te results showed that rats receiving pretest propofol (25 mg/kg) spent signifcantly less time in the target quadrant but showed no change in locomotor activity compared with those in the control group. Memory retrieval was accompanied by reduced phosphorylation of the serine-9 residue of GSK-3β in the hippocampus, whereas phosphorylation of the tyrosine-216 residue was unaffected. However, propofol blocked this retrieval-associated serine-9 phosphorylation. Tese fndings suggest that subhypnotic propofol administration impairs memory retrieval and that the amnestic effects of propofol may be mediated by attenuated GSK-3β signaling in the hippocampus.

Key words: nerve regeneration, glycogen synthase kinase-3β, propofol, memory retrieval, Morris water maze, neural regeneration