Elevated GRIA1 mRNA expression in Layer II/III and V pyramidal cells of the DLPFC in schizophrenia
Elevated GRIA1 mRNA expression in Layer II/III and V pyramidal cells of the DLPFC in schizophrenia
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DOI：
10.1016/j.schres.2007.09.022
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发表时间：
2007-12-01
影响因子：
4.5
通讯作者：
Hemby, S. E.
中科院分区：
文献类型：
--
作者：
O'Connor, J. A.;Hemby, S. E.
精神分裂症患者的背外侧前额皮质（DLPFC）的功能完整性发生改变，导致工作记忆和认知严重缺陷。越来越多的证据表明，谷氨酸信号传导失调可能是介导这些影响的病理生理学的一个重要因素。然而，NMDA 和 AMPA 受体在调节这种缺陷中的作用仍不清楚。关于精神分裂症患者 DLPFC 中离子型谷氨酸受体亚基表达变化的数据的模棱两可，可能反映了该区域内特定神经元群的细胞和分子组成的微妙变化。鉴于先前关于精神分裂症中 II/III 和 V 层锥体细胞改变的证据以及亚基组成对 NMDA 和 AMPA 受体功能的显着影响，激光捕获显微切割结合定量 PCR 用于检测 DLPFC 中 II/III 层和 V 层锥体细胞中 AMPA (GRIA1-4) 和 NMDA (GRIN1、2A 和 2B) 亚基 mRNA 的表达水平。对被诊断患有精神分裂症、双相情感障碍、重度抑郁症的个体和对照组进行比较（n = 15/组）。所有亚基在所有疾病以及对照组的细胞群中均以可检测水平表达。有趣的是，与对照组相比，精神分裂症组两种细胞类型中的 GRIA1 mRNA 均显着增加，而在重度抑郁症（II/III 层和 V 层）和双相情感障碍（V 层）中也观察到类似的趋势。这些数据表明 GRIA1 亚基表达增加可能有助于精神分裂症病理学。 (C) 2007 年由 Elsevier B.V. 出版
The functional integrity of the dorsolateral prefrontal cortex (DLPFC) is altered in schizophrenia leading to profound deficits in working memory and cognition. Growing evidence indicates that dysregulation of glutamate signaling may be a significant contributor to the pathophysiology mediating these effects; however, the contribution of NMDA and AMPA receptors in the mediation of this deficit remains unclear. The equivocality of data regarding ionotropic glutamate receptor alterations of subunit expression in the DLPFC of schizophrenics is likely reflective of subtle alterations in the cellular and molecular composition of specific neuronal populations within the region. Given previous evidence of Layer II/III and V pyramidal cell alterations in schizophrenia and the significant influence of subunit composition on NMDA and AMPA receptor function, laser capture microdissection combined with quantitative PCR was used to examine the expression of AMPA (GRIA1-4) and NMDA (GRIN1, 2A and 2B) subunit mRNA levels in Layer II/III and Layer V pyramidal cells in the DLPFC. Comparisons were made between individuals diagnosed with schizophrenia, bipolar disorder, major depressive disorder and controls (n = 15/group). All subunits were expressed at detectable levels in both cell populations for all diseases as well as for the control group. Interestingly, GRIA1 mRNA was significantly increased in both cell types in the schizophrenia group compare to controls, while similar trends were observed in major depressive disorder (Layers II/III and V) and bipolar disorder (Layer V). These data suggest that increased GRIA1 subunit expression may contribute to schizophrenia pathology. (C) 2007 Published by Elsevier B.V.