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中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (2): 153-156.

• 研究原著 • 上一篇    下一篇

脱氢表雄酮对慢性轻度应激小鼠认知功能的影响

包龙, 杨楠, 刘雁勇, 左萍萍   

  1. 中国医学科学院, 中国协和医科大学基础医学院药理系, 北京 100005
  • 收稿日期:2003-07-08 修回日期:2003-10-28 出版日期:2004-02-26 发布日期:2020-11-16
  • 通讯作者: 左萍萍,女, 教授, 博士生导师, 研究方向:衰老与神经退行性病的药理学。Tel:010-65296404  E-mail: zuopp@public3.bta.net.cn
  • 作者简介:包龙, 男, 医学博士, 现就职于江苏省人民医院骨科。
  • 基金资助:
    国家重点基础研究发展计划基金项目(NO.973,G2000057008)

Effects of dehydroepiandrosterone on cognitive function in mice with chronic mild stress

BAO Long, YANG Nan, LIU Yan-Yong, ZUO Ping-Ping   

  1. Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
  • Received:2003-07-08 Revised:2003-10-28 Online:2004-02-26 Published:2020-11-16

摘要: 目的: 观察慢性轻度应激(CMS) 小鼠模型的自发活动与认知行为变化, 中枢胆碱能毒蕈碱型(M) 受体的改变及药物脱氢表雄酮(DHEA) 的干预作用。方法: 连续3 wk 对小鼠采用7 种不可预知的应激原建立CMS 模型, 设DHEA 低、高两个药物治疗组, 用自发活动和水迷宫法测定行为改变, 用放射性配基法测定皮层、海马、下丘脑和小脑的M 受体改变。结果: CMS 组小鼠自发运动明显减少, 寻找平台潜伏期明显延长, DHEA 补充后可有效改善上述行为变化;CMS 组小鼠大脑皮层、海马的M 受体特异性结合与正常对照组比较显著减少(P<0.05) 。使用DHEA 后, 恢复至正常水平。结论: CMS 可使动物的自发运动减少, 并使其空间学习记忆功能减退,该变化与脑内胆碱能受体活性低下有关。补充DHEA 可有效缓解上述变化, 以低剂量效果好。

关键词: 慢性轻度应激模型, 脱氢表雄酮, M 胆碱能受体, 自发运动, Morris 水迷宫

Abstract: AIM: To investigate the alteration of behavior, such as spontaneous movement, spatial memory ability and cholinergic M receptors in the brain of mice with chronic mild stress (CMS).And to determine whether dehydroepiandrosterone (DHEA) can reverse the cognitive impairment in this model.METHODS: Forty mice were divided into four groups:control group, CMS group, CMS + DHEA low dose (ip, DHEA 5mg·kg-1 ·d-1) group and CMS +DHEA high dose (ip,DHEA 20 mg·kg-1·d-1) group. Morris water maze procedure was used to determine the spatial memory ability and M receptor binding activity was measured with radioactivity assay by 3H-QNB.RESULTS: (1) After 3 weeks in CMS, the spontaneous movement test decreased, and the latency in Morris water maze obviously prolonged. Treating CMS mice with DHEA for 3 weeks could enhance spontaneous movement and latency declined.(2) Whereas the 3H-QNB binding ability to M receptor showed a significantly decrease in cerebral cortex and hippocampus of CMS mice (P<0.05).But decreased ability of M receptor binding was reversed by DHEA treatment in hippocampus (P<0.05).CONCLUSION: DHEA can alleviate the stress response and reverse cognitive impairment induced by CMS, and it may be concerned with the central cholinergic M receptors activity.The studies also show that the low dose of DHEA is better to the CMS model than high dose.

Key words: chronic mild stress (CMS), dehydroepiandrosterone (DHEA), central cholinergic M receptor, spontaneous movement, Morris water maze

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