海马和前脑皮层BDNF和VEGF表达与慢性应激所致小鼠抑郁的相关性

Relationship between chronic stress-induced depression and BDNF/VEGF expression in the mouse hippocampus and forebrain cortex

目的探究海马和前脑皮层脑源性神经营养因子(BDNF)和血管内皮生长因子(VEGF)表达与慢性应激所致小鼠的抑郁的相关性。方法选取SPF级KM小鼠58只,雌雄小鼠各29只。将小鼠随机分为对照组与观察组,观察组小鼠采用禁食、电击足底等多种应激因子刺激,每天随机选择一种,共20 d。对照组小鼠不接受实验应激原,以同样条件饲养。应激前、应激后10 d、20 d均测定小鼠体重。两组小鼠均进行morris水迷宫实验、旷场实验测试,并观察记录结果。测定各组小鼠海马和前脑皮层BDNF和VEGF表达情况,并分析其相关性。结果应激前,两组小鼠体重水平相差不大(P>0.05),应激后,观察组小鼠体重明显低于对照组(P<0.01)。观察组小鼠逃避潜伏期、游泳路程及在第二象限的停留时间明显高于对照组(P<0.05或P<0.01),而在其他象限的停留时间无明显差异(P>0.05)。观察组小鼠修饰次数、垂直运动得分明显低于对照组,中央区停留时间明显高于对照组(P<0.01),排便粒数无明显差异(P>0.05)。与对照组相比,观察组海马CA1区及前脑皮层BDNF、VEGF表达水平明显降低(P<0.05),而两组CA3区BDNF比较差异无统计学意义(P>0.05)。结论慢性应激会导致小鼠出现抑郁样行为,这可能与海马及前脑皮层BDNF和VEGF表达下降有关。

Objective To explore the relationship between expression of brain derived neurotrophic factor(BDNF)and vascular endothelial growth factor(VEGF)in the hippocampus and forebrain cortex and depression induced by chronic stress in mice.Methods We randomly divided 58 SPF KM mice(29 male,29 female)into a control group and observation group.We induced stress in the mice in the observation group via fasting,electric shock,and other techniques.The mice in the control group were not exposed to experimental stressors.We weighed the mice before stress induction,10 days after,and 20 days after stress induction.We then observed and recorded the result of the Morris water maze test and open field test in both groups.We measured BDNF and VEGF expression in the hippocampus and forebrain cortex in each group,and analyzed the correlation.Results Before stress induction,there were no significant differences between the two groups(P>0.05).After stress induction,the mice in the observation group weighed significantly less than those in the control group(P<0.01).The escape latency,swimming distance,and time spent in the second quadrant were significantly higher in the observation group vs.the control group(P<0.05 or P<0.01),but there were no significant differences in the time spent in the other quadrants(P>0.05).The modification times and vertical movement scores of the mice in the observation group were significantly lower than those in the control group,and the retention time in the central area was significantly higher than that in the control group(P<0.01).There was no significant difference in the number of defecation particles(P>0.05).The BDNF and VEGF expression levels in the CA1 area of the hippocampus and forebrain cortex were lower in the observation group vs.control group,but this difference was not significant(P>0.05).Conclusions Chronic stress can induce depressive behavior in mice,which may be related to decreased BDNF and VEGF expression in the hippocampus and forebrain cortex.