Glutamate carboxypeptidase gene expression in the human frontal and temporal lobe in schizophrenia
Glutamate carboxypeptidase gene expression in the human frontal and temporal lobe in schizophrenia
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DOI：
10.1038/sj.npp.1300304
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发表时间：
2004-01-01
影响因子：
7.6
通讯作者：
Kleinman, JE
中科院分区：
文献类型：
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作者：
Ghose, S;Weickert, CS;Kleinman, JE
精神分裂症患者的背外侧前额叶皮层 (DLPFC) 和海马中谷氨酸羧肽酶 II (GCP II) 的活性降低。 GCP II 水解 N-乙酰基-α L-天冬氨酰-L-谷氨酸 (NAAG)，这是哺乳动物大脑中的一种肽，可与 N-甲基 D-天冬氨酸 (NMDA) 受体和 II 类代谢型谷氨酸受体结合，这两种受体都与精神分裂症的病理生理学有关。我们使用原位杂交和银粒检测技术，检测了精神分裂症患者和正常对照死后样本中 DLPFC、内嗅皮层 (ERC) 和海马中 GCP II mRNA 的表达。在神经胶质细胞中检测到 GCP II mRNA。富含胶质的区域，特别是 DLPFC 和 ERC 白质以及海马中的分子层和多态性层，表达高水平的 GCP II mRNA。鉴于早期发现精神分裂症患者大脑中 GCP II 活性降低，我们预计精神分裂症患者中 GCP II mRNA 水平较低。与这一预期相反，我们发现在所检查的大脑区域之一（海马 CA3 多态性区域）中 GCP II mRNA 的表达显着较高。这可能反映了补偿性增加，以纠正 GCP II 活性的降低。我们的研究结果支持这样的观点，即精神分裂症中 NAAG 的水解受到破坏，并且特定的解剖区域可能在 GCP II 合成中表现出离散的异常。
There is decreased activity of glutamate carboxypeptidase II (GCP II) in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of patients with schizophrenia. GCP II hydrolzses N-acetyl-alpha L-aspartyl-L-glutamate (NAAG), a peptide in the mammalian brain that binds to the N-methyl D-aspartate (NMDA) receptor and a group II metabotropic glutamate receptor, both of which have been implicated in the pathophysiology of schizophrenia. We examined the expression of GCP II mRNA in the DLPFC, entorhinal cortex (ERC), and hippocampus in postmortem samples from patients with schizophrenia and normal controls using in situ hybridization followed by silver grain detection. GCP II mRNA was detected in glial cells. Glial-rich regions, specifically the DLPFC and ERC white matter and the molecular and polymorphic layers in the hippocampus, express high levels of GCP II mRNA. Given the earlier finding of decreased GCP II activity in brains of subjects with schizophrenia, we expected to find lower GCP II mRNA levels in schizophrenia. Contrary to this expectation, we found a significantly higher expression of GCP II mRNA in one of the brain areas examined, the hippocampal CA3 polymorphic region. This may reflect a compensatory increase to correct for the decreased activity of GCP II activity. Our findings support the notion that the hydrolysis of NAAG is disrupted in schizophrenia and that specific anatomical regions may show discrete abnormalities in GCP II synthesis.