慢性不可预见性应激模型大鼠海马MAPKs信号蛋白的差异表达

目的 研究慢性不可预见性应激大鼠的认知功能,以及不同的促分裂原活化蛋白激酶(MAPKs)信号蛋白在慢性不可预见性应激大鼠海马的差异表达.方法 32只SD大鼠随机分为正常对照组和慢性不可预见性应激组(CUS),CUS组大鼠每天接受一种应激,共21d,正常对照组不接受任何应激.应激结束后, Morris水迷宫检测空间忆功功能,免疫组织化学和western blot检测MAPKs通路信号蛋白在海马的表达.结果 前5次的定位航行试验,CUS组大鼠找到站台所用的时间显著多于对照组大鼠(F=5.258～10.225,P<0.05),后3次2组大鼠间差异无显著性(F=4.458～4.590,P>0.05);CUS组大鼠在空间探索试中,穿越站台的次数显著少于对照组大鼠(1.8±0.5)次,(7.0±3.9)次,t=3.741,P<0.05].免疫组织化学法示CUS组大鼠齿状回pCREB标记指数显著低于对照组.Western blot示CREB、ERK1、P-ERK1、ERK2、P-ERK2、P38、P-P38和 JNK信号蛋白水平在2组大鼠海马的表达差异无显著性.但CUS组大鼠的P-CREB水平(13.6±8.3)%,(36.0±14.5)%,t=3.792,P<0.05]和P-JNK水平(30.8±7.8)%,(113.8±55.3),t=4.204,P<0.05]显著低于正常对照组.结论 JNK-CREB信号通路异常在21 d 慢性不可预见性应激中起着重要作用.CUS大鼠空间记忆功能是降低的,但通过锻炼,空间忆功功能可以恢复到正常水平.

Differential expression of MAPKs subgroup in the hippocampus of rats exposed to chronic unpredictable stress

Objective To examine the cognitive function and the differential expression of mitogen-activated protein kinase (MAPK) subgroup in the hippocampus of rats exposed to chronic unpredictable stress. Methods Thirty-two SD rats were divided into chronic unpredictable stress (CUS) group and controls. CUS rats were exposed to 21 days chronic unpredictable stressors,and the controls were stress-free. Immediately after the last stressor,the cognitive function was tested using Morris water maze,and the protein levels of MAPK subgroup in hippocampus were detected by immunohistochemistry and western blot. Results The latencies of CUS and control rats differed significantly on the first 5 trial (F=5.258～10.225,P<0.05),but not on the last 3 trial in navigation training (F=4.458～4.590,P>0.05),and the number of times that rats crossed the removed hidden platform in CUS group was significantly fewer than that in the control group (1.8±0.5 VS 7.0±3.9,t=3.741,P<0.05). Immunohistochemistry showed that the labeling index of P-CREB was reduced in the dentate gyrus in CUS group compared with that in the control group. Western blot showed that CREB,ERK1/2,P-ERK1/2,P38,P-P38 and JNK levels had no statistical difference in hippocampus between the two groups. However,CUS significantly decreased P-CREB level (13.6±8.3) % VS (36.0±14.5)%,t=3.792,P<0.05] and P-JNK level (30.8±7.8) % VS (113.8±55.3) %,t=4.204,P<0.05] in the hippocampus. Conclusions Abnormal JNK-CREB cascade played important roles in the CUS,and the spatial memory of the CUS rats was reduced compared to control rats,but can be restored to the comparable level through training.