Elevated neuregulin-1 and ErbB4 protein in the prefrontal cortex of schizophrenic patients
Elevated neuregulin-1 and ErbB4 protein in the prefrontal cortex of schizophrenic patients
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DOI：
10.1016/j.schres.2007.12.474
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发表时间：
2008-03-01
影响因子：
4.5
通讯作者：
Weickert, Cynthia Shannon
中科院分区：
文献类型：
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作者：
Chong, Victor Z.;Thompson, Mia;Weickert, Cynthia Shannon
Neuregulin-1 (NRG1) 及其受体 ErbB4 在基因和转录水平上都与精神分裂症有关。本研究比较了斯坦利联盟的正常、精神分裂症、双相情感障碍和重度抑郁症受试者的前额皮质 (PFC) 细胞质和核部分中的 NRG1 和 ErbB4 蛋白水平。我们使用免疫印迹程序来检查潜在的 NRG1 和 Erb134 免疫反应带，但具体量化了 42、48 和 53 kDa 处的 NRG1 免疫反应信号以及 21、55、60 和 180 kDa 处的 ErbB4 免疫反应信号。相对于其他受试者组，精神分裂症患者 PFC 细胞质 53 kDa NRG1 蛋白水平显着升高（接近 20%）。我们还检测了对 PFC 细胞质全长 (180 kDa) ErbB4 蛋白水平的诊断作用，事后测试表明，相对于正常人和抑郁症受试者，精神分裂症患者的这些数量显着增加（接近 30%）。此外，我们还检查了 PFC 级分中 21、55 和 60 kDa 处的潜在 ErbB4 裂解产物相对于全长 ErbB4 的水平。我们检测了 PFC 细胞质 21 kDa/1 80 kDa 和 55 kDa/1 80 kDa 比率的诊断效果趋势，事后测试表明，与正常人相比，精神分裂症患者的这些比率显着降低。我们的研究表明，与精神分裂症相关的 NRG1 和 ErbB4 mRNA 升高也发生在蛋白质水平，并且可能是精神分裂症所特有的。我们假设 ErbB4 蛋白水解过程也可能在精神分裂症中发生改变，从而产生功能不同形式的 ErbB4 的比例发生改变。由 Elsevier B.V. 出版
Neuregulin-1 (NRG1) and its receptor, ErbB4, have been implicated in schizophrenia at both gene and transcript levels. The present investigation compared NRG1 and ErbB4 protein levels in prefrontal cortical (PFC) cytoplasmic and nuclear fractions among normal, schizophrenic, bipolar and major depressed subjects from the Stanley Consortium. We used immunoblotting procedures to examine potential NRG1 and Erb134 immunoreactive bands, but specifically quantified NRG1 immunoreactive signals at 42, 48 and 53 kDa and ErbB4 immunoreactive signals at 21, 55, 60 and 180 kDa. PFC cytoplasmic 53 kDa NRG1 protein levels were significantly increased (similar to 20%) in schizophrenic patients relative to each of the other subject groups. We also detected diagnostic effects on PFC cytoplasmic full-length (180 kDa) ErbB4 protein levels, and post hoc tests revealed that these quantities were significantly increased (similar to 30%) in schizophrenic patients relative to normal and to depressed subjects. In addition, we examined the levels of potential ErbB4 cleavage products at 21, 55 and 60 kDa relative to those of full-length ErbB4 in the PFC fractions. We detected trends for diagnostic effects on PFC cytoplasmic 21 kDa/1 80 kDa and 55 kDa/1 80 kDa ratios, and post hoc tests revealed that these ratios were significantly reduced in schizophrenic patients relative to normal individuals. Our investigation suggests that schizophrenia-associated NRG1 and ErbB4 mRNA elevations also occur at the protein level and may be specific to schizophrenia. We hypothesize that ErbB4 proteolytic processing may also be altered in schizophrenia, yielding altered ratios of functionally distinct forms of ErbB4. Published by Elsevier B.V.