雄激素对SAMP8小鼠学习记忆能力及海马神经元的影响

EFFECTS OF ANDROGEN ON LEARNING AND MEMORY ABILITY AND HIPPOCAMPUS NEURONS IN SAMP8 MOUSE

目的探讨雄激素对SAMP8小鼠学习记忆能力及海马CA1区神经元的影响。方法7月龄雄性SAMP8小鼠30只,随机分为假手术组、去势组及去势+雄激素补充治疗组。十一酸睾酮(TU)剂量为37.4mg/(kg.15d)。雄激素补充治疗45d后,通过Morris水迷宫观察小鼠学习记忆能力;用苏木素伊红染色,Aβ免疫组织化学及图像分析观察海马CA1区神经元的变化。结果1.Morris水迷宫中,去势组定位航行试验潜伏期明显长于其他组(P<0.05),探索实验跨越平台次数减少(P<0.05)。TU补充治疗能改善学习记忆能力,与假手术组比较差异无统计学意义(P>0.05)。2.去势组海马CA1区弥漫性空泡变性,细胞排列疏松、紊乱,核深染、固缩;Aβ阳性神经元染色深,其数量及吸光度(A)明显高于其他组(P<0.05)。结论去势后,雄激素缺乏可导致学习记忆能力下降,海马神经元严重损伤,雄激素补充治疗可减轻神经元损伤,改善学习和记忆能力。

Objective To explore the effect of androgen on learning and memory ability and neurons in hippocampal CA1 region in senescence accelerated mouse prone strain/8 （SAMP8）. Methods Thirty 7-month-old male SAMP8 were randomly divided into sham-operation control group, castrated group and androgen replacement therapy after castration group. The dose of testosterone undecanoate （TU） was 37.4mg/（ kg· 15d）. The capability of learning and memory was observed 45 days later through the Morris water maze（MWM） test and the change of neurons in hippocampal CA1 region was detected and analyzed by HE staining, immunohistochemal method and computer pathological image analysis system. Results 1. In the MWM test, the escape latency of castrated group were significantly prolonged （ P 〈 0.05 ）. And the times of spanning fiat roof decreased （ P 〈 0.05 ）. Testosterone replacement therapy can improve the learning and memory ability. There was no significant difference from sham- operation control group（ P 〉 0.05）. 2. With HE staining, neurons in hippocampal CAI region of castrated group were found with diffused vacuolar degeneration, and sparse and disordered cellular arranpement. The cell nucleuses were karyochrome and karyopycnosis. The number and optical density of Aβ immune positive neurons were markedly higher than those of other groups（ P 〈 0.05）. Conclusions Androgen deficiency after castraton results in the decreased learning and memory ability and injury in hippocampal neurons. Androgen replacement can lessen the injury and improve the learning and memory ability.