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D-serine enhances fear extinction by increasing GluA2-containing AMPA receptor endocytosis.
Behav Brain Res. 2014 Aug 15; 270:223-7.BB

Abstract

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.

Authors+Show Affiliations

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.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. Electronic address: zfdong@cqmu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24861709

Citation

Bai, Yanrui, et al. "D-serine Enhances Fear Extinction By Increasing GluA2-containing AMPA Receptor Endocytosis." Behavioural Brain Research, vol. 270, 2014, pp. 223-7.
Bai Y, Zhou L, Wu X, et al. D-serine enhances fear extinction by increasing GluA2-containing AMPA receptor endocytosis. Behav Brain Res. 2014;270:223-7.
Bai, Y., Zhou, L., Wu, X., & Dong, Z. (2014). D-serine enhances fear extinction by increasing GluA2-containing AMPA receptor endocytosis. Behavioural Brain Research, 270, 223-7. https://doi.org/10.1016/j.bbr.2014.05.025
Bai Y, et al. D-serine Enhances Fear Extinction By Increasing GluA2-containing AMPA Receptor Endocytosis. Behav Brain Res. 2014 Aug 15;270:223-7. PubMed PMID: 24861709.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - D-serine enhances fear extinction by increasing GluA2-containing AMPA receptor endocytosis. AU - Bai,Yanrui, AU - Zhou,Limin, AU - Wu,Xiaoyan, AU - Dong,Zhifang, Y1 - 2014/05/23/ PY - 2014/03/21/received PY - 2014/05/04/revised PY - 2014/05/09/accepted PY - 2014/5/28/entrez PY - 2014/5/28/pubmed PY - 2015/8/15/medline KW - AMPA receptors KW - Extinction KW - d-Serine SP - 223 EP - 7 JF - Behavioural brain research JO - Behav Brain Res VL - 270 N2 - 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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/24861709/D_serine_enhances_fear_extinction_by_increasing_GluA2_containing_AMPA_receptor_endocytosis_ DB - PRIME DP - Unbound Medicine ER -