N-methyl-D-aspartic acid receptor expression in the dorsolateral prefrontal cortex of elderly patients with schizophrenia
N-methyl-D-aspartic acid receptor expression in the dorsolateral prefrontal cortex of elderly patients with schizophrenia
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DOI：
10.1176/appi.ajp.158.9.1400
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发表时间：
2001-09-01
影响因子：
17.7
通讯作者：
Haroutunian, V
中科院分区：
文献类型：
--
作者：
Dracheva, S;Marras, SAE;Haroutunian, V
目的：由于精神分裂症的某些症状与N-甲基-D-天冬氨酸(NMDA)拮抗剂引起的症状相似，N-甲基-D-天冬氨酸(NMDA)类谷氨酸受体在精神分裂症的病理生理学中受到重视。为了确定NMDA受体在基因水平是否存在异常，检测了老年精神分裂症患者和正常老年患者的前额叶背外侧皮质和枕叶皮质中NMDA受体(NR)亚单位NR1、NR2A和NR2B的表达。方法：将26例死前评估和诊断的老年精神分裂症患者的尸检标本与13例神经病理和神经精神正常的老年对照组(13例)和10例阿尔茨海默病患者(10例)的尸检标本进行比较。用实时定量逆转录聚合酶链式反应检测NR1、NR2A、NR2B亚单位和突触后密度95(PSD-95)的mRNA表达。结果：精神分裂症患者背外侧前额叶皮质和枕叶NR2B亚基的表达高于正常组和阿尔茨海默病组。相比之下，NR1在阿尔茨海默病组的表达明显较低。PSD-95在精神分裂症患者枕叶皮质的表达水平较高，且与NR2A、NR2B在两个皮质区的表达及NR1在枕叶皮质的表达呈显著正相关，与NR1的表达无明显相关性。结论：老年精神分裂症患者存在NMDA受体亚基的异常表达，NR1和NR2A亚单位相对NR2B的不成比例表达可能参与了精神分裂症的病理生理机制以及精神分裂症患者对谷氨酸和谷氨酸能药物的敏感性。
Objective: The N-methyl-D-aspartic acid (NMDA) class of glutamate receptors has received attention in the pathophysiology of schizophrenia because of the similarity between some schizophrenic symptoms and symptoms caused by NMDA antagonists. To determine if NMDA receptor abnormalities were present at the mRNA level, expression of NMDA receptor (NR) subunits NR1, NR2A, and NR2B Was measured in specimens from the dorsolateral prefrontal cortex and the occipital cortex of elderly patients with schizophrenia and normal elderly subjects.Method: Postmortem specimens from antemortem assessed and diagnosed elderly patients with schizophrenia (N=26) were compared with those from a neuropathologically and neuropsychiatrically normal elderly comparison group (N=13) and from patients with Alzheimer's disease (N=10). The mRNA expression of the NR1, NR2A, and NR2B subunits and of postsynaptic density 95 (PSD-95), a protein associated with postsynaptic NMDA receptors, was studied with quantitative real-time reverse transcriptase polymerase chain reaction.Results: Expression of NR1 and NR2A but not NR2B subunits was higher in the dorsolateral prefrontal cortex and the occipital cortex of patients with schizophrenia than in the normal and Alzheimer's disease groups. In contrast, NR1 expression was significantly lower in the Alzheimer's disease group. Occipital cortex expression of PSD-95 was higher in the schizophrenic subjects and correlated strongly with the expression of NR2A and NR2B in both cortical regions and with expression of NR1 in the occipital cortex, These results were not influenced by neuroleptic exposure history, postmortem interval, or age of the subject,Conclusions: NMDA receptor subunits are abnormally expressed in elderly patients with schizophrenia, The disproportionate expression of the NR1 and NR2A subunits relative to NR2B expression may have implications for the pathophysiology of schizophrenia and the sensitivity of schizophrenic patients to glutamate and glutamatergic drugs.