Gene expression profile for schizophrenia - Discrete neuron transcription patterns in the entorhinal cortex
Gene expression profile for schizophrenia - Discrete neuron transcription patterns in the entorhinal cortex
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DOI：
10.1001/archpsyc.59.7.631
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发表时间：
2002-07-01
影响因子：
--
通讯作者：
Eberwine, JH
中科院分区：
文献类型：
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作者：
Hemby, SE;Ginsberg, SD;Eberwine, JH
背景：一些证据表明，包括海马和内嗅皮质（EC）在内的颞叶功能改变与精神分裂症有关。我们使用单细胞基因表达技术来评估EC层11星状神经元中多个基因表达的协调变化，包括神经元信号和突触相关标记。方法：我们采用单神经元显微解剖技术，结合线性反义RNA扩增和高密度/候选基因阵列来评估基因表达的坐标变化。从精神分裂症患者和年龄匹配的对照脑的死后样本的EC层11星状神经元中评估了超过18000个信使rna的表达和相对丰度。初始筛选的结果用于对每个受试者进行更具体的次级信使RNA筛选。结果：数据显示，各种g蛋白偶联受体信号转录物、谷氨酸受体亚基、突触蛋白和其他转录物的表达存在显著差异。二次筛选结果显示，精神分裂症患者星状神经元中g蛋白亚基ialpha1、谷氨酸受体3、n -甲基- d -天冬氨酸受体1、突触素和感觉神经动作电位23、25水平显著降低。我们观察到精神分裂症患者II/II层星状神经元中磷酸化蛋白（一种与阴离子通道形成相关的磷酸化蛋白）信使RNA和蛋白水平下调。结论：这些结果提供了精神分裂症在特定神经元群体中的初步表达谱。了解多种基因在人类疾病中的协同作用，有助于深入了解疾病的分子基础，并为药物治疗干预提供新的靶点。
Background: Several lines of evidence indicate the altered function of the temporal lobe, including the hippocampus and entorhinal cortex (EC), is associated with schizophrenia. We used single-cell gene expression technologies to assess coordinate changes in the expression of multiple genes, including neuronal signaling and synaptic-related markers in EC layer 11 stellate neurons.Methods: We used a single-neuron microdissection technique coupled with linear antisense RNA amplification and high density/candidate gene arrays to assess coordinate changes in gene expression. The expression and relative abundance of more than 18 000 messenger RNAs were assessed from EC layer 11 stellate neurons from postmortem samples of schizophrenic and age-matched control brains. Results of this initial screen were used to perform a more specific secondary messenger RNA screen for each subject.Results: Data disclosed marked differences in expression of various G-protein-coupled receptor-signaling transcripts, glutamate receptor subunits, synaptic proteins, and other transcripts. Results of secondary screening showed significant decreases in levels of G-protein subunit ialpha1, glutamate receptor 3, N-methyl-D-aspartate receptor 1, synaptophysin, and sensory nerve action potentials 23 and 25 in the stellate neurons of schizophrenic patients. We observed down-regulation of phospholemman (a phosphoprotein associated with anion channel formation) messenger RNA and protein levels in layer II/II stellate neurons in the population with schizophrenia.Conclusions: These results provide a preliminary expression profile of schizophrenia in defined neuronal populations. Understanding the coordinated involvement of multiple genes in human disease provides insight into the molecular basis of the disease and offers new targets for pharmacotherapeutic intervention.