Bai Yanrui, Zhou Limin, Wu Xiaoyan, Dong Zhifang
Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
Behav Brain Res. 2014 Aug 15;270:223-7. doi: 10.1016/j.bbr.2014.05.025. Epub 2014 May 23.
Activation of the N-methyl-D-aspartate receptor (NMDAR) glycine site has been shown to enhance memory extinction in physiological and pathological conditions. In the current study, we examined the effects of D-serine, an endogenous NMDAR glycine site agonist, on fear extinction and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) endocytosis in the hippocampus during the process of fear extinction. In inhibitory avoidance task, systemic administration of D-serine (800 mg/kg, i.p.) significantly accelerated memory extinction. The Western blot analyses showed that the acceleration of memory extinction was accompanied by an increase in postsynaptic AMPAR endocytosis in the hippocampus. Furthermore, the application of a synthetic peptide Tat-GluA23Y (3.0 μmol/kg, i.p.) that interferes with the endocytosis of AMPARs succeeded in preventing the enhancement of fear extinction and AMPAR endocytosis induced by D-serine. These results suggest that d-serine might enhance fear extinction through increasing GluA2-containing AMPA receptor endocytosis, and that d-serine may be a potential therapeutic agent against learning and memory disorders.
已证明N-甲基-D-天冬氨酸受体（NMDAR）甘氨酸位点的激活在生理和病理条件下均可增强记忆消退。在本研究中，我们检测了内源性NMDAR甘氨酸位点激动剂D-丝氨酸在恐惧消退过程中对海马体中恐惧消退及α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）内吞作用的影响。在抑制性回避任务中，腹腔注射D-丝氨酸（800 mg/kg）可显著加速记忆消退。蛋白质免疫印迹分析表明，记忆消退的加速伴随着海马体中突触后AMPAR内吞作用的增加。此外，应用干扰AMPARs内吞作用的合成肽Tat-GluA23Y（3.0 μmol/kg，腹腔注射）成功地阻止了D-丝氨酸诱导的恐惧消退增强及AMPAR内吞作用。这些结果表明，D-丝氨酸可能通过增加含GluA2的AMPA受体内吞作用来增强恐惧消退，并且D-丝氨酸可能是一种针对学习和记忆障碍的潜在治疗药物。
