Glutamatergic deficits and parvalbumin-containing inhibitory neurons in the prefrontal cortex in schizophrenia
Glutamatergic deficits and parvalbumin-containing inhibitory neurons in the prefrontal cortex in schizophrenia
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DOI：
10.1186/1471-244x-9-71
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发表时间：
2009-11-16
期刊：
影响因子：
4.4
通讯作者：
Woo, T. U. W.
中科院分区：
文献类型：
--
作者：
Bitanihirwe, B. K. Y.;Lim, M. P.;Woo, T. U. W.
背景资料：我们以前曾报道，N-甲基-D-天冬氨酸（NMDA）类谷氨酸受体NR 2A亚基的信使核糖核酸（mRNA）的表达在精神分裂症大脑皮层的抑制性中间神经元的一个子集减少。在这项研究中，我们试图确定是否在NR 2A mRNA的表达缺陷是目前在亚组的中间神经元，含有钙缓冲小清蛋白（PV），以及这种缺陷是否与减少在前额叶皮层（PFC）在精神分裂症的多巴胺能输入。我们检测了NR 2A mRNA的表达，用S-35标记的核糖探针标记，在表达PV mRNA的神经元中，通过免疫过氧化物酶反应用地高辛标记的核糖探针可视化，在20名精神分裂症患者和20名匹配的正常对照组中。结果：精神分裂症患者PV 3层和4层表达NR 2AmRNA的神经元密度明显降低48-50%，而在PV 3层和4层表达NR 2AmRNA的神经元胞体表达无明显变化。此外，vGluT 1免疫反应终扣的密度显着下降79%，在第3层的PFC在精神分裂症，但在第5层不变。结论：这些研究结果表明，通过NR 2A的NMDA受体PV神经元的PFC精神分裂症可能是缺乏的。这可能解除突触后兴奋回路的抑制，导致精神分裂症中神经元损伤、异常信息流和PFC功能缺陷。
Background: We have previously reported that the expression of the messenger ribonucleic acid (mRNA) for the NR2A subunit of the N-methyl-D-aspartate (NMDA) class of glutamate receptor was decreased in a subset of inhibitory interneurons in the cerebral cortex in schizophrenia. In this study, we sought to determine whether a deficit in the expression of NR2A mRNA was present in the subset of interneurons that contain the calcium buffer parvalbumin (PV) and whether this deficit was associated with a reduction in glutamatergic inputs in the prefrontal cortex (PFC) in schizophrenia.Methods: We examined the expression of NR2A mRNA, labeled with a S-35-tagged riboprobe, in neurons that expressed PV mRNA, visualized with a digoxigenin-labeled riboprobe via an immunoperoxidase reaction, in twenty schizophrenia and twenty matched normal control subjects. We also immunohistochemically labeled the glutamatergic axon terminals with an antibody against vGluT1.Results: The density of the PV neurons that expressed NR2A mRNA was significantly decreased by 48-50% in layers 3 and 4 in the subjects with schizophrenia, but the cellular expression of NR2A mRNA in the PV neurons that exhibited a detectable level of this transcript was unchanged. In addition, the density of vGluT1-immunoreactive boutons was significantly decreased by 79% in layer 3, but was unchanged in layer 5 of the PFC in schizophrenia.Conclusion: These findings suggest that glutamatergic neurotransmission via NR2A-containing NMDA receptors on PV neurons in the PFC may be deficient in schizophrenia. This may disinhibit the postsynaptic excitatory circuits, contributing to neuronal injury, aberrant information flow and PFC functional deficits in schizophrenia.