Synaptic plasticity and characteristics of calcium ion transmembrane flux in hippocampus of 3xTg-AD mice / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To observe the synaptic plasticity and characteristics of transmembrane calcium flux in the hippocampus of 3xTg-AD mice.Methods:According to different genotypes, 6-month-old mice were divided into two groups APP/PS1/tau triple transgenic AD (3xTg-AD) model mice and wild type (WT) mice, with 13 mice in each group.Six mice were randomly selected from each group to do in vivo electrophysiological recording.Field excitatory postsynaptic potential (fEPSP) was evoked by test stimulation, paired-pulse facilitation (PPF) was induced by two stimuli, and long-term potentiation (LTP) was induced by high frequency stimulation (HFS) in the hippocampal CA1 region of mice.The remaining seven mice in each group were used to detect the transmembrane calcium influx and efflux in the slices of hippocampal CA1 region by using non-invasive micro-test technology (NMT). In the electrophysiological and NMT experiments, one mouse fell off respectively.Finally, five mice were enrolled in the electrophysiological experiment and six in the NMT experiment.SPSS 18.0 was used for statistical analysis of all data, and two independent sample t-test was used for comparison between the two groups. Results:(1) In the in vivo electrophysiological experiments, the fEPSP slopes of 3xTg-AD mice and WT mice evoked by test stimulation were stable within 30 min, and the average fEPSP slopes were ((97.8±2.3)%) and ((92.6±12.6)%), respectively.There was no statistical difference of the average fEPSP slopes between the two groups ( t=0.91, P>0.05). After paired-pulse stimulation, the PPF values of 3xTg-AD mice and WT mice were (1.58±0.69) and (1.74±0.17) respectively, and there was no statistical difference between the two groups ( t=0.50, P>0.05). 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)%, t=4.43, P<0.01; (162.5 ±19.7)%, t=5.92, P<0.01). (2) In NMT experiments, the standardized mean and peak velocities of glutamate-induced Ca 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)%, t=6.81, P<0.01; (-917.3±271.7)%, t=4.89, P<0.01). The standardized average and peak velocities of low Ca 2+ solution-induced Ca 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)%, t=2.92, P<0.05; (3 420.4±954.8)%, t=3.31, P<0.01). Conclusion:The hippocampal synaptic plasticity impairment observed in 6-month-old 3xTg-AD may be closely related with the intracellular Ca 2+ overload caused by increased calcium influx and decreased calcium efflux.