Division of Neuroscience Research, Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA.
Transl Psychiatry. 2013 Jun 18;3(6):e271. doi: 10.1038/tp.2013.46.
Fragile X mental retardation protein (FMRP) is an RNA-binding protein that targets ∼5% of all mRNAs expressed in the brain. Previous work by our laboratory demonstrated significantly lower protein levels for FMRP in lateral cerebella of subjects with schizophrenia, bipolar disorder and major depression when compared with controls. Absence of FMRP expression in animal models of fragile X syndrome (FXS) has been shown to reduce expression of gamma-aminobutyric acid A (GABAA) receptor mRNAs. Previous work by our laboratory has found reduced expression of FMRP, as well as multiple GABAA and GABAB receptor subunits in subjects with autism. Less is known about levels for GABAA subunit protein expression in brains of subjects with schizophrenia and mood disorders. In the current study, we have expanded our previous studies to examine the protein and mRNA expression of two novel GABAA receptors, theta (GABRθ) and rho 2 (GABRρ2) as well as FMRP, and metabotropic glutamate receptor 5 (mGluR5) in lateral cerebella of subjects with schizophrenia, bipolar disorder, major depression and healthy controls, and in superior frontal cortex (Brodmann Area 9 (BA9)) of subjects with schizophrenia, bipolar disorder and healthy controls. We observed multiple statistically significant mRNA and protein changes in levels of GABRθ, GABRρ2, mGluR5 and FMRP molecules including concordant reductions in mRNA and proteins for GABRθ and mGluR5 in lateral cerebella of subjects with schizophrenia; for increased mRNA and protein for GABRρ2 in lateral cerebella of subjects with bipolar disorder; and for reduced mRNA and protein for mGluR5 in BA9 of subjects with bipolar disorder. There were no significant effects of confounds on any of the results.
脆性 X 智力低下蛋白（FMRP）是一种 RNA 结合蛋白，它靶向大脑中表达的所有 mRNA 的约 5％。我们实验室的先前工作表明，与对照组相比，精神分裂症、双相情感障碍和重度抑郁症患者的外侧小脑中的 FMRP 蛋白水平显着降低。脆性 X 综合征（FXS）动物模型中 FMRP 的缺失已被证明会降低γ-氨基丁酸 A（GABAA）受体 mRNA 的表达。我们实验室的先前工作发现，自闭症患者的 FMRP 以及多种 GABAA 和 GABAB 受体亚基的表达减少。关于精神分裂症和情绪障碍患者大脑中 GABAA 亚基蛋白表达水平的了解较少。在本研究中，我们扩展了先前的研究，以检查两个新的 GABAA 受体，theta（GABRθ）和 rho 2（GABRρ2）以及 FMRP 和代谢型谷氨酸受体 5（mGluR5）的蛋白和 mRNA 表达在精神分裂症、双相情感障碍、重度抑郁症患者和健康对照组的外侧小脑中，以及在精神分裂症、双相情感障碍和健康对照组患者的额上回（Brodmann 区 9（BA9））中。我们观察到 GABRθ、GABRρ2、mGluR5 和 FMRP 分子的水平在多个mRNA 和蛋白质上发生了显着变化，包括精神分裂症患者的外侧小脑中 GABRθ 和 mGluR5 的 mRNA 和蛋白一致性降低；双相情感障碍患者的外侧小脑中 GABRρ2 的 mRNA 和蛋白增加；以及双相情感障碍患者的 BA9 中 mGluR5 的 mRNA 和蛋白减少。在任何结果中都没有混杂因素的显着影响。
