DECREASED EXPRESSION OF MESSENGER-RNAS ENCODING NON-NMDA GLUTAMATE RECEPTORS GLUR1 AND GLUR2 IN MEDIAL TEMPORAL-LOBE NEURONS IN SCHIZOPHRENIA
DECREASED EXPRESSION OF MESSENGER-RNAS ENCODING NON-NMDA GLUTAMATE RECEPTORS GLUR1 AND GLUR2 IN MEDIAL TEMPORAL-LOBE NEURONS IN SCHIZOPHRENIA
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DOI：
10.1016/0169-328x(94)00247-c
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发表时间：
1995-04-01
期刊：
影响因子：
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通讯作者：
HARRISON, PJ
中科院分区：
文献类型：
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作者：
EASTWOOD, SL;MCDONALD, B;HARRISON, PJ
精神分裂症与大脑谷氨酸能系统的复杂模式改变有关。先前的研究表明，一些海马非 N-甲基-D-天冬氨酸 (non-NMDA) 受体的密度降低，并伴有编码受体 mRNA 的丢失。我们使用原位杂交组织化学技术，在 9 名精神分裂症患者和 14 名匹配的正常对照的左右内侧颞叶切片中使用对两种非 NMDA 受体转录物 GluR1 和 GluR2 具有特异性的寡核苷酸探针，扩展了这项工作。研究发现，精神分裂症患者的海马结构中，双侧 mRNA 均减少，程度相似。放射自显影图分析显示齿状回、CA4、CA3 和下托中 GIuR1 和 GluR2 mRNA 的区域性丢失。海马旁回中的 GluR2 mRNA 也减少。就 S-35 nCi/g 组织当量而言，这些减少范围为 25% 至 70%。此外，我们还测量了每个区域中单个锥体神经元的 mRNA 颗粒密度。精神分裂症患者 CA4 和 CA3 中每个神经元的 GluR1 和 GluR2 mRNA 含量低于对照组。海马旁回神经元中的 GluR2 mRNA 也显着减少，该细胞群中 GluR1 mRNA 与 GluR2 mRNA 的比例增加。在正常或精神分裂症患者的大脑中没有发现 GluR1 和 GluR2 表达的不对称性。这些数据进一步证明了精神分裂症患者内侧颞叶非 NMDA 受体表达减少。他们证实了 GluR1 mRNA 的减少，并表明海马结构中 GluR2 mRNA 也有类似的损失。两种 mRNA 的变化模式表明了一种未知的共同机制，但可能与被认为是该疾病基础的神经发育异常相关。考虑到缺乏 GluR2 亚基的非 NMDA 受体的钙渗透性，精神分裂症患者海马旁回神经元中 GluR2 mRNA 的减少而不是 GluR1 mRNA 的减少可能会产生功能性后果。
Schizophrenia is associated with a complex pattern of alterations in the glutamatergic system of the brain. Previous studies have shown a reduced density of some hippocampal non-N-methyl-D-aspartate (non-NMDA) receptors which is accompanied by a loss of encoding receptor mRNA. We have extended this work using in situ hybridization histochemistry with oligonucleotide probes specific for two non-NMDA receptor transcripts, GluR1 and GluR2, in right and left medial temporal lobe sections from 9 schizophrenics and 14 matched normal controls. Both mRNAs were found to be decreased bilaterally and to a similar degree in the hippocampal formation in schizophrenia. Analysis of autoradiograms showed a regional loss of GIuR1 and GluR2 mRNAs in dentate gyrus, CA4, CA3 and subiculum. GluR2 mRNA was also reduced in parahippocampal gyrus. These reductions ranged from 25% to 70% in terms of S-35 nCi/g tissue equivalents. Additionally we measured grain density for the mRNAs over individual pyramidal neurons in each area. GluR1 and GluR2 mRNAs were less abundant per neuron in CA4 and CA3 in schizophrenia than in controls. GluR2 mRNA was also reduced significantly in parahippocampal gyrus neurons, with an increase in the proportion of GluR1 mRNA to GluR2 mRNA in this cell population. No asymmetries in expression of GluR1 and GluR2 were found in normal or schizophrenic brains. These data further the evidence for reduced non-NMDA receptor expression in the medial temporal lobe in schizophrenia. They confirm the decrease in GluR1 mRNA and show that there are similar losses of GluR2 mRNA in the hippocampal formation. The pattern of changes in the two mRNAs suggests a common mechanism which is unknown but which may be a correlate of the neurodevelopmental abnormalities postulated to underlie the disease. The reduction of GluR2 mRNA but not GluR1 mRNA in parahippocampal gyrus neurons in schizophrenia may have functional consequences given the calcium permeability of non-NMDA receptors lacking the GluR2 subunit.