慢性应激大鼠齿状回的兴奋性氨基酸在空间学习中的变化

Changes of excitatory amino acids in dentate gyrus during spatial learn⁃ing in rats with chronic stress

目的:观察慢性应激(chronic stress,CS)大鼠海马齿状回区(dentate gyrus,DG)的兴奋性氨基酸(ex⁃citatory amino acids,EAAs)及突触传递效应在空间学习记忆过程中的变化,探讨CS影响大鼠空间学习和记忆功能的神经化学机制。方法:16只SD雄性大鼠随机分为对照组和CS组(每组8只),CS组大鼠每天随机给予一种应激刺激,持续30 d,而对照组大鼠不予应激干预。用Morris水迷宫观察大鼠的空间学习和记忆能力,同时用脑部微量透析法和高效液相色谱法测定海马DG区EEAs[(谷氨酸(glutamate,Glu)和天冬氨酸(aspartate,Asp)]含量,并用在体生物电记录法记录同区域的场兴奋性突触后电位(field excitatory postsynaptic potential,fEPSP)幅值。结果:在水迷宫训练过程中,与对照组相比,CS组大鼠在训练第1~4天的逃避潜伏期均显著延长(P<0.05),且第5天观察的目标象限游泳路程百分比显著减少(P<0.05)。在水迷宫训练过程中,对照组大鼠海马DG区的fEPSP幅值及Glu和Asp的水平较训练前逐渐增加后回降(P<0.05),而CS组大鼠DG区的这些指标在整个水迷宫训练过程中均较训练前无显著性变化(P>0.05);与对照组相比,CS组大鼠DG区的fEPSP幅值和Asp水平在水迷宫训练的第3天显著降低,而Glu水平在训练的第2到第4天均显著降低(P<0.05)。结论:慢性应激可通过抑制空间学习过程中的大鼠海马DG区EAAs的增加以及降低突触传递效应,损害大鼠的空间学习与记忆功能。

AIM:To observe the changes of excitatory amino acids(EAAs)and synaptic efficiency in the hip⁃pocampal dentate gyrus(DG)during the spatial learning and memory processes in rats with chronic stress(CS),and to ex⁃plore the neurochemical mechanism of CS affecting spatial learning and memory abilities.METHODS:16 Male SD rats were randomly divided into control group and CS group(8 rats in each group).The rats in CS group randomly received once stressor every day last for 30 days,and the rats in control group were kept for 30 days without stress.The spatial learning and memory abilities of the rats were detected by Morris water maze(MWM).Simultaneously,the concentrations of EAAs(including glutamate and aspartate)in the hippocampal DG were determined by in vivo microdialysis and high performance liquid chromatography,the amplitudes of field excitatory postsynaptic potential(fEPSP)in the same region were examined by electrophysiological recording.RESULTS:In the MWM test,compared with control group,the escape latencies on the 1st~4th days were significantly increased and the percentage of swimming distance in the target quadrant at the 5th day was significantly decreased in CS group(P<0.05).During the MWM test,the fEPSP amplitude and the levels of glutamate and aspartate in the DG were significantly increased and then returned to pre-training levels in control group(P<0.05).In contrast,these parameters were not changed in CS group compared with pre-training levels(P>0.05).In CS group,the fEPSP amplitude and the aspartate level in the DG were decreased at the 3rd day and the glutamate levels in the DG were decreased on the 2nd‒4th days during the MWM test,compared with control group(P<0.05).CONCLU⁃SION:Chronic stress impairs the spatial learning and memory in rats,in part by attenuating the EAAs(including gluta⁃mate and aspartate)responses and synaptic efficiency in the DG during spatial learning.