Ionotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia
Ionotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia
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DOI：
10.1176/appi.ajp.157.11.1811
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发表时间：
2000-11-01
影响因子：
17.7
通讯作者：
Meador-Woodruff, JH
中科院分区：
文献类型：
--
作者：
Ibrahim, HM;Hogg, AJ;Meador-Woodruff, JH
目的：丘脑和谷氨酸功能障碍都与精神分裂症的病理生理有关。作者在精神分裂症患者和对照组的死后样本中检测了嗜离子性谷氨酸受体的表达，使用谷氨酸受体表达的假设；精神分裂症患者丘脑边缘核的差异。方法：测定12例DSM-III-R诊断为精神分裂症的患者和8例精神正常者6个丘脑核中n -甲基- d -天冬氨酸（NMDA）、AMPA和盐酸盐受体的表达。作者采用原位杂交技术测定了NMDAR1、NMDAR2A-NMDAR2D、gluR1-gluR7、KA1和KA2亚基mRNA水平，并采用受体放射自显像法测定了三种受体亚型与谷氨酸结合位点的结合以及与NMDA受体的甘氨酸、多胺和离子通道结合位点的结合。结果：精神分裂症患者丘脑中谷氨酸受体的转录（NMDAR1、NMDAR2B、NMDAR2C、gluR1、gluR3和KA2亚基mrna）和转录后（[H-3]伊芬pro地尔和[H-3]MDL105,519结合NMDA受体的多胺和甘氨酸位点）表达水平均低于对照组，但差异最显著的是在向边缘区域相互映射的核中。结论：边缘丘脑NMDA、AMPA和kainate受体表达异常提示精神分裂症NMDA受体低活性假说，并与精神分裂症丘脑谷氨酸能活性降低相一致。或者，这些结果可能提示传入和/或传出区域的异常谷氨酸神经支配，这些区域是与该疾病有关的边缘结构。这些结果可能为针对嗜离子性谷氨酸受体的抗精神病药物治疗提供神经化学解剖学基础。
Objective: Both thalamic and glutamatergic dysfunction have been implicated in the pathophysiology of schizophrenia. The authors examined ionotropic glutamate receptor expression in postmortem samples from patients with schizophrenia and comparison subjects, using the hypothesis that glutamate receptor expression;differs in limbic nuclei of the thalamus in schizophrenia.Method: N-Methyl-D-aspartate (NMDA), AMPA, and kainate receptor expression was determined in six thalamic nuclei from 12 subjects with DSM-III-R diagnoses of schizophrenia and eight psychiatrically normal individuals. The authors used in situ hybridization to determine NMDAR1, NMDAR2A-NMDAR2D, gluR1-gluR7, KA1, and KA2 subunit mRNA levels and receptor autoradiography to determine binding to glutamate binding sites of the three receptor subtypes and to the glycine, polyamine, and ion channel binding sites of the NMDA receptor.Results: Glutamate receptor expression was lower at both transcriptional (NMDAR1, NMDAR2B, NMDAR2C, gluR1, gluR3, and KA2 subunit mRNAs) and posttranscriptional ([H-3]ifenprodil and [H-3]MDL105,519 binding to polyamine and glycine sites of the NMDA receptor) levels in the thalamus in patients with schizophrenia than in comparison subjects, but differences were most prominent in nuclei with reciprocal projections to limbic regions.Conclusions: Abnormalities in NMDA, AMPA, and kainate receptor expression in limbic thalamus are suggestive of the NMDA receptor hypoactivity hypothesis of schizophrenia and are consistent with diminished glutamatergic activity in the thalamus in schizophrenia. Alternatively, these results could suggest abnormal glutamatergic innervation in afferent and/or efferent regions, which are limbic structures that have been implicated in this illness. These results may provide a neurochemical anatomical substrate for antipsychotic therapies targeting ionotropic glutamate receptors.