APP/PS1双转基因小鼠认知功能和实时步态行为相关性研究

目的初步探讨APP/PS1双转基因小鼠认知功能和实时步态行为学的改变的相关性。方法 3月龄APP/PS1转基因小鼠16只随机分成模型组和石杉碱甲片组,正常对照组选用同龄C57/BL6J小鼠14只。连续治疗150 d,Morris水迷宫(MWM)检测学习记忆能力,大小鼠步态分析仪(GAS-2)检测实时步态行为,并比较两种行为学的相关性。结果与正常对照相比,模型组小鼠有学习记忆能力的显著降低,逃避潜伏期均显著延长(P0.05),在目标象限停留时间、游泳路程显著降低(P0.05),第一次穿越平台的时间显著延长(P0.05),穿台次数显著减少(P0.05);在步态行为实验中,模型组小鼠平均步行速度显著降低(P0.05),平均步行周期、绝对值平均体转角和侧向移动均显著升高(P0.05),在一个步行周期中左后足(left foot,LF)、右后足(right foot,RF)支撑时相显著延长(P0.05),摆动时相显著缩短(P0.05),左前足(left hand,LH)、右前足(right hand,RH)、右后足推进指数均显著增加(P0.05),制动指数显著降低(P0.05)。石杉碱甲片能显著改善认知功能,并能在一定程度上纠正步态行为的变化。比较两种行为学的相关性,得出学习记忆能力与双前足的制动指数相关性较高(相关系数分别为-0.433、-0.379,P值分别为0.039、0.079),其他方面的相关性不大。结论 APP/PS1转基因小鼠在8月龄时有显著的学习记忆能力障碍和步态行为的改变,并且两种行为学存在一定的相关性。

To explore the relationship between the gait behavior changes and cognitive function in APP/PS1 transgenic mice

Objective To explore the relationship between the gait behavior changes and cognitive function in APP/PS1 transgenic mice. Methods 16 APP/PS1 transgenic mice were divided into model group and Huperzine A group, C57/BL6J mice with the same age were chosed as control group. After a 150 days consecutive treatment, Morris water maze(MWM) was used to detect the learning and memory ability and Gait analysis system (GAS-2) was used to detect the gait behavior after the treatment when the mice were 8-month-old. Results The escape latency of the model group was significantly higher than that of the control group (P< 0.05), the time spended in the target quadrant, swimming distance in the target quadrant significantly lower than that of the control group (P< 0.05), the first time passing through the platform prolonged significantly than the control group (P< 0.05), and the number of passing though the platform reduced significantly than the control group (P< 0.05). In the gait behavior experiments, compared with the control group, the average walking speed of the model group reduced significantly (P< 0.05), the average walking cycle, the absolute average body angle and lateral movement increased significantly (P< 0.05); The percentage of support time in a walking cycle of the left and right foot increased significantly (P< 0.05). Accordingly, the percentage of swing time in a walking cycle of the left and right foot reduced significantly (P< 0.05). The propulsion index of the left hand, right hand, right foot increased significantly (P< 0.05), and then the braking index of the above three feet decreased significantly (P< 0.05). Huperzine A can improve the cognitive function, rectify the changes in the gait behavior. The two behavioral relevance shows that cognitive function and the front two feet braking, propulsion index have a high correlation index (correlation coefficients were -0.433, -0.379, P values were 0.039,0.079), the others were not. Conclusion APP/PS1 transgenic mice of 8-months-old have a remarkable impairment of learning and memory ability and disorder of gait behavior, and these two behaviors have a correlation in some extent.