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

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

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。

ObjectiveIn the present experiment we investigate the behavior of 4- month- oldtransgenic APP/PS-1/tau mice model with Alzheimer＇s disease（3 × Tg-AD mice） to evaluate their abilities ofspatial learning and memory. We observe the changes of synaptic plasticity and soluble amyloid-β protein42（Aβ42） expression in the CA1 region of hippocampus to explore the mechanism of early cognitiveimpairment of 3 × Tg-AD mice.MethodsTen 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 wereconducted to observe emotion disorder and ability of spatial learning and memory. Field excitatorypostsynaptic potential（f EPSP） and theta burst stimulation（TBS）-induced long-term potentiation（LTP） wererecorded in CA1 region of hippocampus. The expression changes of soluble Aβ42in hippocampus weremeasured by enzyme-linked immunosorbent assay（ELISA）.ResultsThe open field test showed that therewas no significant differences between 3 × Tg-AD group and control group, which indicated that there wasno obvious anxiety tendency in 4-month-old 3 × Tg-AD mice. Compared with control group, 3 × Tg-ADgroup mice had significantly longer escape latency from the 3rd to 5th day（P = 0.001, 0.003, 0.001） andlower percentage of time through the platform area（P = 0.000）. LTP induced by TBS in CA1 region ofhippocampus of 3 × Tg-AD group decreased significantly（P 0.01, for all） compared with that of controlgroup. In contrast to control group, the expression of soluble Aβ42in the hippocampus of 3 × Tg-AD mice group increased significantly（P = 0.000）.ConclusionsThe expression of soluble Aβ42in the hippocampusof 4-month-old 3 × Tg-AD mice increased significantly, which impaired synaptic plasticity in CA1 region ofhippocampus and led to a significant decline in spatial learning and memory ability.