双氢睾酮对快速老化小鼠海马CA1区突触可塑性和N-甲基-D-天冬氨酸受体1的影响

Effects of dihydrotestosterone on synaptic plasticity and the expression of N-methyl-D-aspartate receptor 1 in CA1 region of hippocampus in SAMP8 mouse

目的探讨双氢睾酮(DHT)对快速老化小鼠(SAMP8)海马CA1区突触可塑性和N-甲基-D-天冬氨酸受体1(NMDAR1)的影响。方法 6月龄雄性SAMP8小鼠21只随机分为假手术组、去势组及去势+DHT补充治疗组,每组7只。DHT剂量为1mg/(kg.d),皮下注射21d后,通过Golgi染色观察海马CA1区顶树突树突棘的变化;免疫组织化学及图像分析检测突触素和NMDAR1表达的改变。结果 1.Golgi染色,去势组海马CA1区顶树突树突棘个数明显减少;DHT补充治疗后,树突棘个数明显增多。2.去势组海马CA1区突触素和NMDAR1的表达明显减少,平均吸光度值明显低于其他组(P<0.05)。DHT补充治疗能明显增加突触素和NMDAR1的表达。结论 DHT可调节海马CA1区突触可塑性,使树突棘密度增多。DHT对突触可塑性的影响可能与其调节锥体细胞的NMDAR1有关。

Objective To explore the effects of dihydrostestosterone （DHT） on synaptic plasticity and the expression of N-methyl-D-aspartate receptor 1 （NMDAR1） in CA1 region of hippocampus in senescence accelerated mouse prone strain 8 （SAMP8）. Methods Twenty-one 6-month-old male SAMP8 were randomly divided into sham-operation control group, castrated group and DHT replacement therapy after castration group（7 in each group）. The dose of DHT was 1mg/（kg.d） . Twenty-one days later, the apical dendritic thorns density in hippocampal CA1 region was observed with Golgi staining method. Immunohistochemieal method and computer pathological image analysis system were used to determine the expression of synaptophysin and N-methyl-D-aspartate 1 （ NMDAR1 ） in hippocampal CA1 region. Results 1. In the Golgi staining, the number of the apical dendritic thorns density of hippocampal CA1 region of castrated group decreased. However, DHT replacement therapy could significantly increase the apical dendritic thorns density （P 〈 0.05 ）. 2. The expressions of synaptophysin and NMDAR1 in the hippocampal CA1 region of castrated group decreased markedly. The average ahsorbanee （ AA ） values were sharply lower than those of other groups （ P 〈 0.05 ）. DHT replacement therapy could obviously increase the expression of synaptophysin and NMDAR1 in the hippoeampal CA1 region. Conclusion DHT replacement therapy can increase the density of dendritic thorns and modulate synaptic plasticity of hippocampal CA1 region. DHT may potentially affect hippoeampal synaptic plasticity by modulating pyramidal cell NMDARI.