运动训练对小鼠空间学习记忆能力及海马神经发生的影响

摘要

Objective To investigate the effects of regular and irregular mandatory treadmill running (TR) on learning and memory abilities,stress response,survival and maturation of newborn neurons in dentate area of C57 mice. Methods Forty-eight male C57BL/6 mice were randomly divided into regular running group (n=16,definite time and quantity), irregular running group (n=16,definite time and different quantities) and sedentary group (n=16).Injection of bromodeoxyuridine (BrdU,50 mg/kg) was given intraperitoneally to mice from the 1st d to the 7th d of exercise,and then,these mice were subjected to a 4-wk TR training course or sedentary exercise.Double irnmunofluorescence labeling was employed to observe the effect of TR on survival and maturation of newborn neurons. Mice were trained on the Morris water maze to test the abilities of learning and memory. Corticosterone (CORT).level in the venous blood was measured with a radioimmunoassay kit. Results As compared with that in mice of the irregular running group and sedentary group,significant decrease of latency was noted in mice of the regular running group on the 1st, 3rd, 4th and 5th d of place navigation test (P＜0.05). As compared with that in mice of the sedentary group, significant decrease of latency was noted in mice of the irregular running group and regular running group on the 2nd d of place navigation test (P＜0.05),while no significant difference of that was noted between mice of the irregular running group and regular running group (P＞0.05).The platform was removed for a 60-s probe test 4 h after the last trial to test the recall ability, and the times of staying in the target zone in each group were regular running group＞irregular running group＞control group, and significant difference was noted between each 2 groups (P＜0.05). The numbers of double immunofluorescence labeled cells in the dentate gyrus were counted as regular running group＞irregular running group＞control group, and significant difference was noted between each 2 groups (P＜0.05). The serum CORT level was measured as regular running group＜irregular running group＜control group, and significant difference was noted between each 2 groups (P＜0.05). Conclusion Mandatory treadmill running could improve the learning and memory abilities,which may be related to the increment of survival and maturation of neural precursor cells,and decreased level of serum CORT; and the effect of regular mandatory treadmill running is better than that of irregular mandatory treadmill running.%目的 观察规律和不规律的中度强迫运动对小鼠学习记忆能力、应激反应、海马齿状回新生神经前体细胞的存活及成熟的影响. 方法 将48只C57BL/6雄性小鼠按照随机数字表法分为3组,A组为规律运动训练组(n=16,定时定量),B组为不规律运动训练组(n=16,定时不定量),C组为对照组(n=16).对A、B组小鼠进行为期4周的强迫运动训练,C组小鼠不做运动训练.从正式训练第1天起对3组动物进行腹腔溴脱氧尿嘧啶核苷(BrdU)注射(50 mg/kg),连续标记7d.免疫荧光双标法观察各组小鼠海马齿状回区BrdU与神经元核心抗原(NeuN)双标记的情况.同时采用Morris水迷宫检测小鼠空间学习记忆能力,放射性免疫法检测小鼠静脉血皮质醇含量. 结果 定位航行实验中,第1、3、4、5天,A组小鼠潜伏期较B、C组均大幅度降低,差异有统计学意义(P＜0.05)；第2天A、t3组小鼠潜伏期均较C组小鼠有明显降低,差异有统计学意义(P＜0.05),其中A、B组小鼠差异无统计学意义(P＞0.05).空间探索实验中,3组小鼠在平台象限时间长短比较结果为A组＞B组＞C组,差异均有统计学意义(P＜0.05).3组小鼠海马齿状回区BrdU和NeuN双阳性细胞数比较结果为A组＞B组＞C组,差异均有统计学意义(P＜0.05).3组小鼠静脉血皮质醇含量比较结果为A组＜B组＜C组,差异均有统计学意义(P＜0.05). 结论运动训练能增强小鼠学习记忆能力,其中规律运动训练较不规律运动训练更有效,推测与两种运动形式促进海马新生神经前体细胞存活数目、分化成熟程度、血皮质醇水平降低程度不同有关.