Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression.
Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression.
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DOI：
10.1016/j.pnpbp.2008.10.005
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发表时间：
2009-02-01
影响因子：
5.6
通讯作者：
Karolewicz, Beata
中科院分区：
文献类型：
--
作者：
Feyissa, Anteneh M.;Chandran, Agata;Stockmeier, Craig A.;Karolewicz, Beata
关键词：
最近的神经影像学和尸检研究表明，在重性抑郁症的多巴胺能传递异常。谷氨酸NMDA（N-甲基-D-天冬氨酸）受体是中枢神经系统兴奋性神经传递的主要介质之一。在突触部位，NMDA受体与突触后密度蛋白-95（PSD-95）连接，PSD-95在受体激活后介导运输、聚集和下游信号传导事件中起关键作用。本研究采用Western blot方法检测了大鼠前额叶皮层（PFC）NMDA受体亚单位NR 1、NR 2A、NR 2B和PSD-95的表达。皮质样本来自年龄、性别和死后间隔匹配的抑郁症和精神健康对照组。结果显示，与对照组相比，抑郁受试者PFC中NMDA受体亚基NR 2A（−54%）和NR 2B（−48%）的表达以及PSD-95蛋白水平（−40%）降低，而NR 1亚基没有变化。NMDA受体亚单位，特别是NR 2A和NR 2B，以及PSD-95的改变表明，在PFC的NMDA受体信号异常，在抑郁症。我们的研究结果结合最近的临床，细胞和神经影像学研究进一步暗示谷氨酸神经传递参与抑郁症的病理生理。这项研究提供了额外的证据，NMDA受体复合物是一个目标，发现新的抗抑郁药。
Recent neuroimaging and postmortem studies have demonstrated abnormalities in glutamatergic transmission in major depression. Glutamate NMDA (N-methyl-D-aspartate) receptors are one of the major mediators of excitatory neurotransmission in the central nervous system. At synaptic sites, NMDA receptors are linked with postsynaptic density protein-95 (PSD-95) that plays a key role in mediating trafficking, clustering, and downstream signaling events, following receptor activation. In this study, we examined the expression of NMDA receptor subunits NR1, NR2A, and NR2B as well as PSD-95 in the anterior prefrontal cortex (PFC) using Western blot method. Cortical samples were obtained from age, gender and postmortem interval matched depressed and psychiatrically healthy controls. The results revealed that there was a reduced expression of the NMDA receptor subunits NR2A (−54%) and NR2B (−48%), and PSD-95 protein level (−40%) in the PFC of depressed subjects relative to controls, with no change in the NR1 subunit. The alterations in NMDA receptor subunits, especially the NR2A and NR2B, as well as PSD-95 suggest an abnormality in the NMDA receptor signaling in the PFC in major depression. Our findings in conjunction with recent clinical, cellular, and neuroimaging studies further implicate the involvement of glutamate neurotransmission in the pathophysiology of depression. This study provides additional evidence that NMDA receptor complex is a target for discovery of novel antidepressants.
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DOI：
10.1017/s1461145708008985
发表时间：
2009-03-01
影响因子：
4.8
作者：
Karolewicz, Beata;Szebeni, Katalin;Ordway, Gregory A.
通讯作者：
Ordway, Gregory A.
影响因子：
10.6
作者：
Berman, RM;Cappiello, A;Krystal, JH
通讯作者：
Krystal, JH
影响因子：
10.6
作者：
Auer, DP;Pütz, B;Holsboer, F
通讯作者：
Holsboer, F
影响因子：
25
作者：
Hardingham, GE;Fukunaga, Y;Bading, H
通讯作者：
Bading, H
影响因子：
--
作者：
Cotter, D;Mackay, D;Everall, I
通讯作者：
Everall, I