The role of the tripartite glutamatergic synapse in the pathophysiology and therapeutics of mood disorders.
The role of the tripartite glutamatergic synapse in the pathophysiology and therapeutics of mood disorders.
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DOI：
10.1177/1073858409336093
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Zarate CA
中科院分区：
文献类型：
--
作者：
Machado-Vieira R;Manji HK;Zarate CA
双相情感障碍（BPD）和重度抑郁症（MDD）是常见的慢性复发性心境障碍，影响着全球数百万人的生活。越来越多的证据表明，多巴胺能系统功能障碍直接参与心境障碍。本文介绍了“三重突触”的作用，包括突触前和突触后神经元和胶质细胞，在情绪障碍的病理生理和治疗。谷氨酸能神经元和神经胶质通过整合效应直接控制突触和突触外谷氨酸水平/释放，这些效应靶向谷氨酸兴奋性氨基酸转运蛋白、突触后密度蛋白、离子型受体（α-氨基-3-羟基-5-甲基异恶唑（AMPA）、N-甲基-D-天冬氨酸（NMDA）和红藻氨酸（KA））和代谢型受体（mGluRs）。本文还探讨了阿片类调节剂利鲁唑和氯胺酮，这被认为是开发下一代抗抑郁药和情绪稳定剂的有价值的概念验证剂。在治疗相关范例中，氯胺酮优先靶向突触后AMPA/NMDA受体，利鲁唑优先靶向突触前电压操作通道和神经胶质。
Bipolar disorder (BPD) and major depressive disorder (MDD) are common, chronic, and recurrent mood disorders that affect the lives of millions of individuals worldwide. Growing evidence suggests that glutamatergic system dysfunction is directly involved in mood disorders. This article describes the role of the “tripartite glutamatergic synapse”, comprising presynaptic and postsynaptic neurons and glial cells, in the pathophysiology and therapeutics of mood disorders. Glutamatergic neurons and glia directly control synaptic and extrasynaptic glutamate levels/release through integrative effects that target glutamate excitatory amino-acid transporters, postsynaptic density proteins, ionotropic receptors (alpha-amino-3-hydroxy-5-methylisoxazole (AMPA), N-methyl-D-aspartate (NMDA), and kainate (KA)), and metabotropic receptors (mGluRs). This article also explores the glutamatergic modulators riluzole and ketamine, which are considered valuable proof of concept agents for developing the next generation of antidepressants and mood stabilizers. In therapeutically relevant paradigms, ketamine preferentially targets postsynaptic AMPA/NMDA receptors, and riluzole preferentially targets presynaptic voltage-operated channels and glia.
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