存在突触发生和NMDA受体作中作为潜在的精神疾病潜在靶点的谷氨酸盐信号

Title:Glutamate Signaling in Synaptogenesis and NMDA Receptors as Potential Therapeutic Targets for Psychiatric Disorders

Volume: 15 Issue: 3

Author(s): Y. Ohgi, T. Futamura and K. Hashimoto

Affiliation:

关键词: 动物模型，谷氨酸盐，情感障碍，NMDA受体，后期研究，精神分裂症，脊柱密度

摘要: Glutamate, a major excitatory neurotransmitter, plays important roles in synaptic plasticity, such as long-term potentiation (LTP) and new synapse formation. Growing evidence suggests that glutamate signaling is involved in the neurobiology of psychiatric disorders, including schizophrenia, major depressive disorder (MDD) and bipolar disorder (BP). Postmortem brain studies demonstrated altered spine density in brains from patients with these psychiatric disorders, indicating that remodeled neuronal circuits may contribute to the pathobiology of these psychiatric diseases. Drugs targeting the glutamate system have typically attracted attention as they show efficacy in animal studies and potential therapeutic effects in the clinical setting. In particular, the Nmethyl- D-aspartate (NMDA) receptor antagonist, ketamine exerts a rapid and robust antidepressant effect in treatment-resistant patients with MDD and BP, whereas conventional antidepressants require several weeks for therapeutic onset. Animal studies showed that ketamine induced rapid synaptogenesis, suggestive of synaptic plasticity via NMDA receptor signaling being an essential event in the treatment of depression. Therefore, drugs modulating glutamate signaling could also be potential therapeutic drugs for psychiatric disorders. First, we summarize the role of glutamate signaling on dendritic spine formation, maintenance and remodeling. Then, we discuss the abnormalities identified in dendritic spine and glutamate signaling from postmortem brain studies and animal models of psychiatric disorders. Finally, we review the potential benefits of drugs acting on the NMDA receptor in clinical and animal models of psychiatric disorders.

Cite this article as:

Y. Ohgi, T. Futamura and K. Hashimoto , Glutamate Signaling in Synaptogenesis and NMDA Receptors as Potential Therapeutic Targets for Psychiatric Disorders, Current Molecular Medicine 2015; 15 (3) . https://dx.doi.org/10.2174/1566524015666150330143008