Decreased expression of NMDA receptor-associated proteins in frontal cortex of elderly patients with schizophrenia.
Decreased expression of NMDA receptor-associated proteins in frontal cortex of elderly patients with schizophrenia.
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DOI：
10.1097/wnr.0b013e32832d30d9
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发表时间：
2009-07-15
期刊：
影响因子：
1.7
通讯作者：
Meador-Woodruff JH
中科院分区：
文献类型：
--
作者：
Funk AJ;Rumbaugh G;Harotunian V;McCullumsmith RE;Meador-Woodruff JH
越来越多的证据表明，在精神分裂症的突触后密度中，激活就绪的n-甲基-d-天冬氨酸（NMDA）受体复合物过少。突触后密度蛋白95 （PSD95）、突触gtpase激活蛋白（SynGAP）和多PDZ结构域蛋白（MUPP1）是NMDA受体信号复合物的组成部分，有助于促进信号传导、运输和稳定。我们假设涉及这些分子的缺陷可能有助于精神分裂症的病理生理。为了验证我们的假设，我们测量了PSD95、SynGAP和MUPP1在前扣带皮层和背外侧前额皮质中的蛋白表达。我们发现PSD95在前扣带皮层的表达减少。抗精神病药物分析显示，与对照组相比，停药患者前扣带皮层SynGAP表达减少。这些数据提示NMDA受体复合物的形成、定位和下游信号可能在精神分裂症中异常。
Converging evidence suggests too few activation-ready N-methyl-d-aspartic acid (NMDA) receptor complexes in the postsynaptic density in schizophrenia. Postsynaptic density protein 95 (PSD95), Synaptic GTPase-activating protein (SynGAP), and Multiple PDZ domain protein (MUPP1) are integral components of the NMDA receptor signaling complex, and help facilitate signaling, trafficking, and stabilization. We hypothesized that deficits involving these molecules may contribute to the pathophysiology of schizophrenia. To test our hypothesis, we measured protein expression of PSD95, SynGAP, and MUPP1 in the anterior cingulate cortex and dorsolateral prefrontal cortex. We found decreased PSD95 expression in the anterior cingulate cortex. Antipsychotic medication analyses showed decreased SynGAP expression in the anterior cingulate cortex in patients off medication when analyzed against our comparison group. These data suggest that NMDA receptor complex formation, localization, and downstream signaling may be abnormal in schizophrenia.