NMDA受体在焦虑症发病机制的研究进展

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。

Research Progress of NMDA Receptors in the Mechanisms of AnxietyDisorder

Anxiety disorder is a common mental illness. With the growing social pressure, the incidence of this disease has beenrising gradually. The pathogenesis of anxiety is very complex and has not yet been fully elucidated. The aim of this paper is to review therecent progress of different subtypes of NMDA receptors and pharmaceutical intervention via different mechanisms related to anxietydisorder. NMDA receptors are mainly distributed in the brain, spinal cord and peripheral nervous system. NR1 is widely expressed in thecentral nervous system. In NR2D mutant mice, the interaction of NR1 and NR2D may be involved in anxiety-like behavior. NR2A andNR2B are two important subunits of NMDA receptors. In the plus-maze, ifenprodil, the NMDA receptor polyamine site antagonist had ananxiolytic profile which was accompanied by an increase in locomotion. The replacement of subunit NR2C by NR2B in juvenile miceshowed increased open arm avoidance in the elevated plus-maze and increased fear-induced immobility, which indicated that NR2B andNR2C may be involved in the occurrence of anxiety. Further clarification for the exact mechanism of regulation of NMDA receptorsubunits will help to explore the potential therapeutic target of anxiety disorders and promote the targeted research and development ofnew drugs for anxiety disorders.