Objective To explore the apoptosis in the hippocampus of dysbindin-1B+/+ mice and the behaviors of 4-month-old dysbindin-1B+/+ mice and wild-type mice. Methods The hippocampus of dysbindin-1B+/+ mice and corresponding wild-type mice were assessed by TUNEL assay and transmission electron microscopy. Then twelve 4-month-old male dysbindin-1B+/+ mice and twelve wild-type mice were enrolled. The open field and T maze test were conducted to observe locomotor activity,exploratory behaviors,and spatial memory. Result TUNEL+ neurons were found in hippocampus of dysbindin-1B+/+ mice,especially in dentate gyrus region,but not in that of wild-type mice(t=12.98,P<0.0001). Transmission electron microscopy showed the presence of middle-and late-stage apoptosis in the hippocampus of dysbindin-1B+/+ mice,while there was no apoptosis in wild-type mice. Open field test showed that,compared with the moving distance of wild-type mice [(3632±606)cm],dysbindin-1B+/+ mice presented significantly lower moving distances [(2887±376)cm] (t=2.993,P=0.0122). Meanwhile,compared with the moving time of wild-type mice in the central area [(114.00±34.09)s],dysbindin-1B+/+ mice presented lower moving time [(64.22±14.67)s] (t=4.649,P=0.0023). T maze test showed that when the interval between forced run and test run were 60 s and 180 s,respectively,the accuracy of dysbindin-1B+/+ was (70.40±15.17)% and (59.28±9.10)%,which was significantly lower than those of wild type mice (91.67±13.94)% (t=3.261,P=0.0258) and (83.33±14.89)% (t=3.687,P=0.0291);when the interval was 15 s,there was no significant difference between these two groups [100% vs.(94.45±6.08)%;t=0.851,P=0.0756]. Conclusion Dysbindin-1B+/+ expression can cause the apoptosis of neurons,which may cause anxious behavior and impair the locomotor activity and spatial memory.%目的 观察人源特异性表达dysbindin-1B+/+(dys1B)小鼠的组织学及行为学表现.方法 建立dys1B转基因小鼠,采用TUNEL法检测野生型(WT)和dys1B小鼠海马脑区凋亡情况,并在电镜下观察WT和dys1B小鼠海马区的凋亡情况,旷场实验和T迷宫实验观测小鼠在新环境中的自主活动能力、焦虑程度及空间记忆能力.结果 dys1B小鼠海马区神经元凋亡率明显高于WT小鼠(t=12.98,P<0.0001),且在电镜下有凋亡中期和晚期表现.旷场实验结果显示,dys1B小鼠的总运动距离为(2887±376)cm,明显低于WT小鼠的(3632±606)cm(t=2.993,P=0.0122);中心活动时间为(64.22±14.67)s,明显少于WT小鼠的(114.00±34.09)s(t=4.649,P=0.0023).T迷宫实验结果显示,forced run与test run间隔60和180 s时,dys1B小鼠的正确率分别为(70.40±15.17)%和(59.28±9.10)%,明显低于WT小鼠的(91.67±13.94)%(t=3.261,P=0.0258)和(83.33±14.89)%(t=3.687,P=0.0291);间隔15 s时,dys1B小鼠和WT小鼠的正确率差异无统计学意义[100%比(94.45±6.08)%;t=0.851,P=0.0756].结论 dys1B表达可引起小鼠海马区细胞凋亡并可导致自主活动能力降低,焦虑程度增加,空间记忆能力障碍.
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