周吉银 周世文 曾圣雅 汤建林 徐颖.NMDA受体在焦虑症发病机制的研究进展[J].,2016,16(6):1184-1186 |
NMDA受体在焦虑症发病机制的研究进展 |
Research Progress of NMDA Receptors in the Mechanisms of AnxietyDisorder |
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DOI: |
中文关键词: 焦虑症 NMDA受体 亚型 进展 |
英文关键词: Anxiety disorder NMDA receptor Subtype Progress |
基金项目:重庆市科委自然科学基金一般项目(CSTC, 2009BB5323);
国家十一五重大新药创制科技重大专项军队特需药品保密专项课题(2009ZXJ09004-062) |
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中文摘要: |
伴随社会生活和工作压力的增大,常见精神类疾病焦虑症的发病率逐年攀升。焦虑症的发病机制非常复杂,迄今尚未完全
阐明。本文概述了焦虑症发病机制与NMDA受体不同亚型的关系。NMDA受体主要广泛分布于脑、脊髓和周围神经系统。NR1
广泛分布于中枢神经,在NR2D亚基敲除小鼠中,NR1 和NR2D 的相互影响可能参与了焦虑样行为。NR2A 与NR2B是NMDA
受体的两个重要亚基,NR2B的高选择性拮抗剂艾芬地尔在小鼠的高架十字迷宫实验中发挥了抗焦虑功效。将小鼠全脑的NR2C
基因用NR2B 替代之后,1月龄变异小鼠的高架十字迷宫实验显示有明显的非条件性焦虑行为,表明NR2B和NR2C 均可能参与
焦虑的发生。因此,深入阐明调控NMDA受体亚基组成的确切作用机制,将有助于探索焦虑症潜在治疗靶点的发现,并针对性地
开展新药的研发。 |
英文摘要: |
Anxiety disorder is a common mental illness. With the growing social pressure, the incidence of this disease has been
rising gradually. The pathogenesis of anxiety is very complex and has not yet been fully elucidated. The aim of this paper is to review the
recent progress of different subtypes of NMDA receptors and pharmaceutical intervention via different mechanisms related to anxiety
disorder. NMDA receptors are mainly distributed in the brain, spinal cord and peripheral nervous system. NR1 is widely expressed in the
central nervous system. In NR2D mutant mice, the interaction of NR1 and NR2D may be involved in anxiety-like behavior. NR2A and
NR2B are two important subunits of NMDA receptors. In the plus-maze, ifenprodil, the NMDA receptor polyamine site antagonist had an
anxiolytic profile which was accompanied by an increase in locomotion. The replacement of subunit NR2C by NR2B in juvenile mice
showed increased open arm avoidance in the elevated plus-maze and increased fear-induced immobility, which indicated that NR2B and
NR2C may be involved in the occurrence of anxiety. Further clarification for the exact mechanism of regulation of NMDA receptor
subunits will help to explore the potential therapeutic target of anxiety disorders and promote the targeted research and development of
new drugs for anxiety disorders. |
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