NMDA Receptor and Schizophrenia: A Brief History
NMDA Receptor and Schizophrenia: A Brief History
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DOI：
10.1093/schbul/sbs076
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发表时间：
2012-09-01
影响因子：
6.6
通讯作者：
Coyle, Joseph T.
中科院分区：
文献类型：
--
作者：
Coyle, Joseph T.
尽管谷氨酸在20世纪80年代首次被假设参与了精神分裂症的病理生理，但证明n -甲基- d -天冬氨酸（NMDA）受体拮抗剂（解离麻醉剂）可以在正常受试者中复制精神分裂症的精神、消极、认知和生理特征的全部范围，使“NMDA受体功能减退假说”有了坚实的基础。另一项研究表明，在接受抗精神病药物治疗的精神分裂症患者中，多种增强甘氨酸调节部位NMDA受体功能的药物显著减轻了阴性症状，并不同程度地改善了认知能力。最后，NMDA受体的持续阻断在实验动物中重现了精神分裂症的关键病理特征，包括小蛋白阳性皮质gaba能神经元的下调、锥体神经元树突状发育不良和脊柱密度降低。
Although glutamate was first hypothesized to be involved in the pathophysiology of schizophrenia in the 1980s, it was the demonstration that N-methyl-D-aspartate (NMDA) receptor antagonists, the dissociative anesthetics, could replicate the full range of psychotic, negative, cognitive, and physiologic features of schizophrenia in normal subjects that placed the "NMDA receptor hypofunction hypothesis" on firm footing. Additional support came from the demonstration that a variety of agents that enhanced NMDA receptor function at the glycine modulatory site significantly reduced negative symptoms and variably improved cognition in patients with schizophrenia receiving antipsychotic drugs. Finally, persistent blockade of NMDA receptors recreates in experimental animals the critical pathologic features of schizophrenia including downregulation of parvalbumin-positive cortical GABAergic neurons, pyramidal neuron dendritic dysgenesis, and reduced spine density.