Chinese Journal of Contemporary Neurology and Neurosurgery ›› 2015, Vol. 15 ›› Issue (5): 406-410. doi: 10.3969/j.issn.1672-6731.2015.05.012

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Study on early cognitive function in transgenic APP/PS-1/tau mice model of Alzheimer's disease

WANG Li1, JIAO Jin-song1, LIU Zun-jing1, GU Wei-hong1, SHUI Yuan2, YAMAMOTO Ryo3, KATO Nobuo3   

  1. 1Department of Neurology, 2Pain Management Center, China-Japan Friendship Hospital, Beijing 100029, China
    3Department of Physiology, Kanazawa Medical University, Kanazawa 920-0293, Ishikawa, Japan
  • Online:2015-05-25 Published:2015-05-22
  • Contact: KATO Nobuo (Email: kato@kanazawa-med.ac.jp)
  • Supported by:

    This study was supported by the National Natural Science Foundation of China for Young Scholars (No. 81300942).

APP/PS-1/tau 三转基因阿尔茨海默病模型小鼠早期认知功能研究

王丽, 焦劲松, 刘尊敬, 顾卫红, 水源, 山本亮, 加藤伸郎   

  1. 100029 北京,中日友好医院神经内科(王丽、焦劲松、刘尊敬、顾卫红),疼痛诊疗研究中心(水源);920-0293 日本金沢医科大学生理学系(山本亮,加藤伸郎)
  • 通讯作者: 加藤伸郎(Email:kato@kanazawa-med.ac.jp)
  • 基金资助:

    国家自然科学基金青年科学基金资助项目(项目编号:81300942)

Abstract:

Objective  In the present experiment we investigate the behavior of 4-month-old transgenic APP/PS-1/tau mice model with Alzheimer's disease (3 × Tg-AD mice) to evaluate their abilities of spatial learning and memory. We observe the changes of synaptic plasticity and soluble amyloid-β protein 42 (A β 42) expression in the CA1 region of hippocampus to explore the mechanism of early cognitive impairment of 3 × Tg-AD mice.  Methods  Ten 4-month-old male 3 × Tg-AD mice and matched ten 129/C57BL/6 hybrid wild type (WT) mice were enrolled. The open field test and Morris water maze test were conducted to observe emotion disorder and ability of spatial learning and memory. Field excitatory postsynaptic potential (fEPSP) and theta burst stimulation (TBS)-induced long-term potentiation (LTP) were recorded in CA1 region of hippocampus. The expression changes of soluble A β 42 in hippocampus were measured by enzyme-linked immunosorbent assay (ELISA).  Results The open field test showed that there was no significant differences between 3 × Tg-AD group and control group, which indicated that there was no obvious anxiety tendency in 4-month-old 3 × Tg-AD mice. Compared with control group, 3 × Tg-AD group mice had significantly longer escape latency from the 3rd to 5th day (P = 0.001, 0.003, 0.001) and lower percentage of time through the platform area (P = 0.000). LTP induced by TBS in CA1 region of hippocampus of 3 × Tg-AD group decreased significantly (P < 0.01, for all) compared with that of control group. In contrast to control group, the expression of soluble Aβ42 in the hippocampus of 3 × Tg-AD mice group increased significantly (P = 0.000).  Conclusions  The expression of soluble Aβ42 in the hippocampus of 4-month-old 3 × Tg-AD mice increased significantly, which impaired synaptic plasticity in CA1 region of hippocampus and led to a significant decline in spatial learning and memory ability.

Key words:

摘要:

目的 观察APP/PS-1/tau 三转基因阿尔茨海默病(3 × Tg-AD)模型小鼠空间学习和记忆能力、海马CA1 区突触可塑性和可溶性β-淀粉样蛋白42(Aβ42)表达变化,探讨3 × Tg-AD 小鼠早期认知功能障碍发生机制。方法 4 月龄雄性3 × Tg-AD 小鼠和相匹配的129/C57BL/6 杂交野生型小鼠各10 只,旷场实验和Morris 水迷宫实验观察小鼠在新环境中的焦虑程度和自主活动能力,以及空间学习和记忆能力;记录海马CA1 区场兴奋性突触后电位和高频强直电刺激诱导的长时程增强;酶联免疫吸附试验检测海马组织可溶性Aβ42 表达变化。结果 与对照组相比,3 × Tg-AD 组小鼠旷场实验结果无明显改变(均P > 0.05),定位航行实验第3 ~ 5 天逃避潜伏期延长(P = 0.001,0.003,0.001),空间探索实验穿越平台区时间百分比降低(P = 0.000),海马CA1 区高频强直电刺激诱导的长时程增强下降(均P < 0.01),海马组织可溶性Aβ42 表达水平升高(P = 0.000)。结论 4 月龄3 × Tg-AD 小鼠海马组织可溶性Aβ42 表达上调,导致海马CA1区突触可塑性受损,出现空间学习和记忆能力下降。

关键词: 阿尔茨海默病, 认知障碍, 突触, 淀粉样β蛋白, 疾病模型, 动物