慢性束缚应激对老龄大鼠空间学习和记忆能力及海马齿状回区兴奋性氨基酸水平的影响

摘要

Objective:To explore the effects of chronic restraint stress (CRS) on the abilities of spatial learning and memory and the levels of excitatory amino acids in the hippocampal dentate gyrus (DG) in the old rats,and to investigate the neurochemical mechanism of CRS in affecting the spatial learning and memory abilities.Methods:Sixteen male SD rats (18 months old) were randomly divided into control group (n =8) and CRS group (n=8),and the rats in CRS group received CRS 2 h every day for 30 d.And then the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test,and the extracellular levels of excitatory amino acids including asparate (Asp) and glutamate (Glu) in the DG were simultaneously determined by in vivo microdialysis and HPLC.The levels of corticosterone (CORT) and epinephrine (EPI) in serum of the rats wereexamined by ELISA assay.Results:In CRS group,the escape latencies on the 2nd-4th days were significantly increased and the percentage of time spent in target quadrant on the 5th day was markedly decreased in MWM test compared with control group (P＜0.05).Compared with before training,the extracelluar level of Asp in the DG in control group was significantly increased on the 2nd day in MWM test;compared with control group,the extracelluar level of Asp in the DG in CRS group was significantly decreased on the 3rd day in MWM test (P＜0.05).Compared with before training,the Glu levels in the DG in MWM test in both control and CRS groups were markedly increased (P＜0.05),but there was no significant difference between two groups (P＞0.05).Compared with control group,the levels of CORT and EPI in the serum of the rats in CRS group were significantly increased (P＜0.05).Conclusion:CRS impairs the spatial learning and memory abilities in the old rats,which may be related to the decrease of Asp level in the hippicampal DG of the rats.%目的:探讨慢性束缚应激(CRS)对老龄大鼠学习和记忆能力及海马齿状回(DG)区兴奋性氨基酸水平的影响,初步阐明CRS影响空间学习和记忆能力的部分神经化学机制.方法:16只18月龄SD雄性大鼠随机分为对照组和CRS组(每组8只),CRS组大鼠每天给予2h的CRS,连续30 d.利用Morris水迷宫(MWM)实验检测CRS大鼠空间学习记忆能力,采用脑部微量透析法和高效液相色谱法检测在MWM实验过程中大鼠海马DG区兴奋性氨基酸[谷氨酸(Glu)和天冬氨酸(Asp)]水平,采用酶联免疫法测定大鼠血清中皮质酮(CORT)和肾上腺素(EPI)水平.结果:MWM实验,与对照组比较,CRS组第2～4天大鼠逃避潜伏期明显延长(P＜0.05),且第5天在目标象限游泳的时间明显减少(P＜0.05).与训练前比较,对照组大鼠海马DG区Asp水平在MWM实验第2天明显增加(P＜0.05);与对照组比较,CRS组大鼠DG区Asp水平在MWM实验第3天明显下降(P＜0.05);与训练前比较,在MWM实验过程中2组大鼠海马DG区Glu水平均明显增加(P＜0.05),但2组间比较差异无统计学意义(P＞0.05).与对照组比较,CRS组大鼠血清中CORT和EPI水平明显升高(P＜0.05).结论:CRS降低老年大鼠的空间学习和记忆能力,这可能与大鼠海马DG区Asp水平降低有关.