海马齿状回神经再生对WKY大鼠抑郁样行为的影响

Effects of neurogenesis in the dentate gyrus(DG)of hippocampus on depression-like behaviors in WKY rats

目的:观察海马齿状回(DG)神经再生对成年Wistar Kyoto(WKY)大鼠抑郁样行为的影响。方法:实验共分三个组(n=10):①正常对照(Wistar)组:选取9周龄Wistar大鼠,给予生理盐水3周(10 mg/kg,灌胃);②抑郁模型(WKY)组:选取同龄WKY大鼠并经行为学测定后筛选出抑郁大鼠作为抑郁模型组,给予生理盐水3周(10 mg/kg,灌胃);③阳性对照(AMI+WKY)组:选取同龄WKY抑郁大鼠,给予阿米替林(AMI)3周(10 mg/kg,灌胃)。选用免疫荧光染色细胞增殖标记物Ki67、未成熟神经元标志物DCX检测大鼠的海马神经再生水平;应用糖水偏好实验(SPT)、旷场实验(OFT)和强迫游泳实验(FST)检测各组大鼠的抑郁样行为学变化。结果:①WKY抑郁大鼠海马DG区细胞增殖标志物Ki67+细胞数和未成熟神经元标志物DCX+细胞数较Wistar大鼠分别降低了33.0%(P<0.01)和39.2%(P<0.01);阿米替林给药后使抑郁大鼠海马DG区Ki67+细胞数和DCX+细胞数分别增加了43.8%(P<0.01)和46.7%(P<0.01)。②与Wistar大鼠相比,WKY抑郁大鼠糖水偏好程度明显降低(P<0.01),旷场实验中运动总距离显著缩短(P<0.01)和中心停留时间显著减少(P<0.01),强迫游泳实验中不动时间明显延长(P<0.01);阿米替林治疗可显著改善WKY大鼠的上述抑郁样行为。结论:①成年WKY抑郁大鼠的海马神经干细胞的增殖和分化能力较正常对照组显著降低,提示成年WKY抑郁大鼠的神经再生受损;②改善海马受损的神经再生可以部分逆转成年WKY大鼠的抑郁样行为。

Objective:To observe the effects of the neurogenesis in the dentate gyrus(DG)of the hippocampus on depression-like behaviors in adult Wistar Kyoto(WKY)rats.Methods:There were three groups in total(n=10):①the control(Wistar)group:9-week-old Wistar rats were treated with saline for 3 weeks(10 mg/kg,intragastric administration);②the depression model(WKY)group:WKY rats of the same age,tested for depression-like behaviors,were as a rat model of depression,and were treated with saline for 3 weeks(10 mg/kg,intragastric administration);③the positive control(AMI+WKY)group:WKY rats of the same age were treated with amitriptyline for 3 weeks(10 mg/kg,intragastric administration).The neurogenesis in hippocampus was detected by immunofluorescence staining for Ki67(a neuronal proliferation marker)and DCX(an immature neuronal marker).The depression-like behaviors were assessed by sucrose preference test(SPT),open field test(OFT)and forced swimming test(FST).Results:①When compared with Wistar rats,the number of Ki67+cells and DCX+cells of the DG in WKY rats were decreased by 33.0%(P<0.01)and 39.2%(P<0.01),respectively;amitriptyline treatment significantly increased the number of Ki67+cells and DCX+cells in the DG by 43.8%(P<0.01)and 46.7%(P<0.01),respectively,as compared with WKY rats.②When compared with control group,WKY rats showed a significant decrease in sucrose preference(P<0.01),less total horizontal distance(P<0.01)and less time entered the center field(P<0.01)in the OFT,the immobility time in the FST was increased significantly(P<0.01).Amitriptyline treatment significantly improved the depression-like behaviors in WKY rats.Conclusion:①The proliferation and differentiation of hippocampal neural stem cells in adult WKY rats are significantly lower than those of Wistar rats,suggesting that the neurogenesis in adult WKY rats is impaired.②Amelioration of impaired hippocampal neurogenesis can partially reverse the depression-like behaviors in adult WKY rats.