Elevated levels of NR2A and PSD-95 in the lateral amygdala in depression
Elevated levels of NR2A and PSD-95 in the lateral amygdala in depression
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DOI：
10.1017/s1461145708008985
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发表时间：
2009-03-01
影响因子：
4.8
通讯作者：
Ordway, Gregory A.
中科院分区：
文献类型：
--
作者：
Karolewicz, Beata;Szebeni, Katalin;Ordway, Gregory A.
令人信服的证据表明，重度抑郁症与大脑谷氨酸能传递功能障碍有关，谷氨酸能n -甲基- l天冬氨酸（NMDA）受体在抗抑郁活性中起作用。最近的尸检研究表明，抑郁症与大脑中与NMDA受体信号相关的蛋白质浓度的改变有关。本研究调查了抑郁症受试者杏仁核中的谷氨酸信号蛋白，为抑郁症的杏仁核病理提供了强有力的证据。研究人员从13-14对年龄、性别和死后时间间隔匹配的抑郁症和精神健康对照者身上获得侧杏仁核样本。Western免疫印迹法检测NMDA受体NR1、NR2A亚基以及NMDA受体相关蛋白如突触后密度蛋白-95 （PSD-95）和神经元一氧化氮合酶（nNOS）的浓度。此外，在相同的杏仁核样本中测量了参与谷氨酸代谢的酶的水平，包括谷氨酰胺合成酶和谷氨酸脱羧酶（GAD-67）。与对照组相比，抑郁症患者NR2A蛋白水平显著升高（+115%,p=0.03）。有趣的是，与对照组相比，相同抑郁受试者的PSD-95水平也高（+128%,p=0.01）。NRI、nNOS、谷氨酰胺合成酶和GAD-67的量不变。NR2A和PSD-95水平的升高表明杏仁核NMDA受体的谷氨酸信号在抑郁症中被破坏。
Compelling evidence suggests that major depression is associated with dysfunction of the brain glutamatergic transmission, and that the glutamatergic N-methyl-L aspartate (NMDA) receptor plays a role in antidepressant activity. Recent post-mortem studies demonstrate that depression is associated with altered concentrations of proteins associated with NMDA receptor signalling in the brain. The present study investigated glutamate signalling proteins in the amygdala from depressed subjects, given strong evidence for amygdala pathology in depression. Lateral amygdala samples were obtained from 13-14 pairs of age- sex-, and post-mortem-interval-matched depressed and psychiatrically healthy control subjects. Concentrations of NR1 and NR2A subunits of the NMDA receptor, as well as NMDA receptor-associated proteins such as post-synaptic density protein-95 (PSD-95) and neuronal nitric oxide synthase (nNOS) were measured by Western immunoblotting. Additionally, levels of enzymes involved in glutamate metabolism, including glutamine synthetase and glutamic acid decarboxylase (GAD-67), were measured in the same amygdala samples. NR2A protein levels were markedly and significantly elevated (+115%, p=0.03) in depressed subjects compared to controls. Interestingly, PSD-95 levels were also highly elevated (+128%, p=0.01) in the same depressed subjects relative to controls. Amounts of NRI, nNOS, glutamine synthetase, and GAD-67 were unchanged. Increased levels of NR2A and PSD-95 suggest that glutamate signalling at the NMDA receptor in the amygdala is disrupted in depression.