摘要/Abstract
摘要： 目的·探讨选择不同的测试指标和观测时段是否影响情景条件恐惧实验对5XFAD转基因小鼠学习和记忆能力的检测效力。方法·选用雄性5XFAD转基因小鼠与雌性C57BL/6小鼠交配繁殖的4月龄雌性子代5XFAD小鼠12只为实验组，同窝Littermates小鼠（LM小鼠）14只为对照组，相继进行旷场实验及情景条件恐惧实验。分别采用旷场实验中的总路程、速度及情景条件恐惧实验训练阶段前60 s的平均运动指数，评估2组小鼠的自发活动性有无差异。继而分别选取测试阶段前180 s、181～360 s或前300 s作为观测时段，评估不同观测时段下小鼠僵直时间百分比和活动抑制率，并进一步探究选择不同观测时段对2种检测指标的差异性检出效力的影响。结果·2组小鼠在旷场实验中的总路程和速度比较，差异均无统计学意义；但其情景条件恐惧实验训练阶段前60 s的平均运动指数间比较，差异有统计学意义（P=0.027）。LM小鼠不同观测时段僵直时间百分比的差异有统计学意义（均P<0.05），而活动抑制率的差异无统计学意义；5XFAD小鼠不同观测时段僵直时间百分比和活动抑制率的差异均无统计学意义。在3个观测时段观察小鼠的运动状态时，2组小鼠僵直百分比的差异均无统计学意义；选取测试阶段的前180 s观测时，5XFAD小鼠的活动抑制率明显高于LM小鼠（P=0.038）；而在其余2个观测时段中，2组小鼠活动抑制率的差异无统计学意义。结论·采用情景条件恐惧实验训练阶段的平均运动指数检测5XFAD小鼠的自发活动性较旷场实验的总路程和速度更敏感。在情景条件恐惧实验中，观测时段的不同设定可对单一品系小鼠的僵直时间百分比产生影响，而不影响活动抑制率。选用活动抑制率较僵直时间百分比更能准确反映出5XFAD小鼠的认知功能障碍，将测试阶段的前180 s作为观测时段更为准确。
关键词: 阿尔茨海默病, 5XFAD转基因小鼠, 旷场实验, 情景条件恐惧实验, 观测时段
Abstract:
Objective · To explore whether different test indicators and observation periods in contextual fear conditioning test affect the detection effectiveness of learning and memory ability of 5XFAD transgenic mice. Methods · Twelve 4-month-old female 5XFAD transgenic progeny mice and 14 4-month-old female LM progeny mice were selected, which were produced by crossing male 5XFAD transgenic mice and female C57BL/6 mice, to conduct open field test and contextual fear conditioning test in succession. Total distance and velocity in open field test and average motion index in the first 60 s of training stage in contextual fear conditioning test of the two groups of mice were used to evaluate the difference of locomotor activity. Besides, the first 180 s, 181-360 s and the first 300 s of testing stage for observation were selected to evaluate the selection effects on percent freeze and activity suppression ratio. Then further investigation was launched to explore the effects of different observation periods on the detection effectiveness of percent freeze and activity suppression ratio. Results · The differences of total distance and total velocity of the two groups of mice in open field test were not statistically significant, however the average motion index in the first 60 s of training stage in contextual fear conditioning test of 5XFAD transgenic mice was significantly higher than that of LM mice (P=0.027). The comparison of percent freeze among the three groups of observation periods of LM mice had significant difference (both P<0.05), while there was no statistical significance in activity suppression ratio. The comparisons of percent freeze and activity suppression ratio among the three groups of observation periods of 5XFAD mice had no significant difference. The differences of percent freeze between 5XFAD mice and LM mice was not statistically significant during the three observation periods. However, the activity suppression ratio of 5XFAD mice was significantly higher than that of LM mice in the first 180 s (P=0.038), in the other two observation periods the difference of activity suppression ratio between the two groups of mice was not statistically significant. Conclusion · The average motion index detected in training stage in contextual fear conditioning test is more sensitive than total distance and total velocity detected in open field test for evaluating locomotor activity of 5XFAD mice. In contextual fear conditioning test, different observation periods have effects on the value of percent freeze provided by single strain of mice, while the value of activity suppression ratio remains unaffected. Activity suppression ratio is more precise than percent freeze to reflect the cognitive deficiency of 5XFAD mice. It is more accurate to select the first 180 s of testing stage for observation.
Key words: Alzheimer’s disease (AD), 5XFAD transgenic mouse, open field test, contextual fear conditioning test, observation period
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