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目的:观察3xTg-AD小鼠海马突触可塑性与钙离子跨膜流动特征。方法:根据基因型不同,将6月龄小鼠分为APP/PS1/tau三转基因AD(3xTg-AD)模型小鼠和野生型(WT)对照组小鼠两组,每组13只。每组随机选取6只小鼠进行在体电生理记录,给予测试刺激记录其海马CA1区场兴奋性突触后电位(field excitatory postsynaptic potential,fEPSP)、配对脉冲刺激记录双脉冲易化(paired-pulse facilitation,PPF)、高频刺激(high frequency stimulation,HFS)诱导长时程增强(long-term potentiation,LTP)。每组剩余的7只小鼠采用非损伤微测技术(non-invasive micro-test technology,NMT),检测海马CA1区脑片神经元的跨膜钙内流和钙外排情况。3xTg-AD小鼠在电生理和NMT实验中各损失1只,最终入组电生理实验5只,NMT实验6只。采用SPSS 18.0对所有数据进行统计学分析,两组间比较使用两独立样本n t检验。n 结果:(1)在体电生理实验中,给予测试刺激后30 min内,3xTg-AD小鼠和WT小鼠的fEPSP斜率均比较稳定,其平均fEPSP斜率分别为[(97.8±2.3)%]和[(92.6±12.6)%],两组之间差异无统计学意义(n t=0.91,n P>0.05);给予配对脉冲刺激后,3xTg-AD小鼠和WT小鼠的PPF值分别为(1.58±0.69)和(1.74±0.17),两组间差异无统计学意义(n t=0.50,n P>0.05);给予HFS后30 min和60 min,3xTg-AD小鼠的LTP值分别为[(104.9±10.9)%]和[(98.0±10.8)%],明显低于WT小鼠的[(156.5±21.3)%](n t=4.43,n P0.05). At 30 min and 60 min post-HFS, the LTP values in 3xTg-AD mice were ((104.9±10.9)%) and ((98.0±10.8)%) respectively, which were significantly lower than those in WT mice((156.5±21.3)%,n t=4.43, n P<0.01; (162.5 ±19.7)%,n t=5.92, n P<0.01). (2) In NMT experiments, the standardized mean and peak velocities of glutamate-induced Can 2+ influx in hippocampal CA1 region of 3xTg-AD mice were ((-2 166.0±425.0)%) and ((-3 539.6±1 270.9)%) respectively, which were significantly higher than those in WT mice((-735.3±262.9)%, n t=6.81, n P<0.01; (-917.3±271.7)%,n t=4.89, n P<0.01). The standardized average and peak velocities of low Can 2+ solution-induced Can 2+ efflux in 3xTg-AD mice were ((1 451.6±297.1)%) and ((1 968.7±227.3)%) respectively, which were significantly lower than those in WT mice((2 579.3±810.9)%, n t=2.92, n P<0.05; (3 420.4±954.8)%,n t=3.31, n P<0.01).n Conclusion:The hippocampal synaptic plasticity impairment observed in 6-month-old 3xTg-AD may be closely related with the intracellular Can 2+ overload caused by increased calcium influx and decreased calcium efflux.n