上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

西酞普兰对APP23小鼠学习记忆及Aβ神经性病变的影响

周维涛1,2，黄道超1,2，钟海英1,3，赵 丽1,3   

  1. 重庆医科大学附属儿童医院 1.儿科研究所 儿童发育疾病研究教育部重点实验室， 2.儿科学重庆市重点实验室， 3.重庆市儿童发育重大疾病诊治与预防国际科技合作基地， 重庆 400014
  • 出版日期:2015-02-28 发布日期:2015-02-27
  • 通讯作者: 赵 丽, 电子信箱: lilily_333@sina.com。
  • 作者简介:周维涛（1989—）， 男， 住院医师， 硕士; 电子信箱: zhouweitao_2008@126.com。

Effects of citalopram on learning, memory, and Aβ neuropathies of APP23 transgenic mice

ZHOU Wei-tao1,2, HUANG Dao-chao1,2, ZHONG Hai-ying1,3, ZHAO Li1,3   

  1. 1.Department of Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, 2.Chongqing Key Laboratory of Pediatrics, 3.Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014,  China
  • Online:2015-02-28 Published:2015-02-27

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摘要：

目的 探讨早期给予低剂量西酞普兰对阿尔茨海默病（AD）小鼠学习记忆和β淀粉样蛋白（Aβ）病理性变化的影响。方法 将5月龄APP23转基因小鼠30只随机分为西酞普兰组和对照组，每组15只。西酞普兰组给予西酞普兰10 mg/kg腹腔注射，对照组腹腔注射等容量的生理盐水，连续3个月。最后一次药物干预后24 h行Morris水迷宫实验，测定小鼠空间学习与记忆能力。水迷宫实验结束后断头取脑，ELISA法检测脑组织中Aβ40和Aβ42水平，免疫组织化学检测老年斑数量，Western blotting检测海马Aβ前体（APP）、β位分解酶1 （BACE1）和β-C末端片段（β-CTF）C99/C89的表达水平。结果 与对照组比较，西酞普兰组小鼠隐蔽平台逃避潜伏期明显缩短，活动总路径减少，穿越平台次数增加（P<0.05）；西酞普兰组小鼠脑组织内Aβ40和Aβ42水平明显低于对照组，老年斑数量明显减少（P<0.05），但APP、BACE1和β-CTF蛋白表达未见明显改变（P>0.05）。结论 早期低剂量长疗程给予西酞普兰干预可改善AD小鼠空间学习记忆能力，减轻Aβ神经性病变，其机制可能与西酞普兰上调α分泌酶水平、促进APP在该切割途径代谢增强有关。

关键词: 西酞普兰, 学习记忆, 阿尔茨海默病

Abstract:

Objective To investigate the effects of administration of low dose citalopram in early stage on the learning, memory, and pathological changes of amyloid β-protein (Aβ) of mice with Alzheimer disease (AD). Methods Thirty 5-month-old APP23 transgenic mice were randomly divided into the citalopram group (n=15) and control group (n=15). Mice of the citalopram group were intraperitoneally injected with 10 mg/kg citalopram for 3 months and mice of the control group were intraperitoneally injected with the same volume of normal saline for 3 months. Morris water maze test was adopted to determine the learning and memory functions 24 h after the final injection. Mice were sacrificed and brain tissues were obtained after the final Morris water maze test. Aβ40 and Aβ42 levels of brain tissues were detected by the ELISA. The amount of senile plaques was counted by the immunohistochemical staining. The expression levels of amyloid precursor protein (APP), β-site APP-cleaving enzyme (BACE1), and β-CTF C99/C89 of hippocampus tissues were determined by the Western blotting. Results Compared to the control group, the escape latency of the citalopram group was significantly shorter; total swimming distance decreased; the number of crossing the platform increased (P<0.05); Aβ40 and Aβ42 levels were significantly lower; and the number of senile plaques significantly decreased (P<0.05). But the expressions of APP, BACE1, and β-CTF did not change significantly (P>0.05). Conclusion Long-term administration of low dose citalopram in early stage can improve the learning and memory functions of mice with AD and decrease Aβ neuropathies. The mechanism may be relevant to the up-regulation of expression of α-secretase and enhancing the metabolism of APP in this splicing pathway by citalopram.

Key words: citalopram, learning and memory, Alzheimer disease