Decreased expression of reelin receptor VLDLR in peripheral lymphocytes of drug-naive schizophrenic patients
Decreased expression of reelin receptor VLDLR in peripheral lymphocytes of drug-naive schizophrenic patients
复制标题
DOI：
10.1016/j.schres.2007.09.029
复制
发表时间：
2008-01-01
影响因子：
4.5
通讯作者：
Mori, Norio
中科院分区：
文献类型：
--
作者：
Suzuki, Katsuaki;Nakamura, Kazuhiko;Mori, Norio
Reelin是一种分泌性蛋白酶，在神经发育和突触可塑性中起主要作用，也可能在精神分裂症的发病机制中起作用。本研究旨在探讨两种受体的reelin，极低密度脂蛋白受体（VLDLR）和载脂蛋白E受体2型（ApoER 2）的表达，是否异常的精神分裂症患者外周血淋巴细胞。在这项研究中，我们测量了精神分裂症患者（未接受药物治疗的患者（n = 20）和接受药物治疗的患者（n = 20））以及年龄和性别匹配的健康对照（n = 40）的血液淋巴细胞中V-LDLR和ApoER 2的mRNA水平。使用定量实时RT-PCR。此外，我们研究了mRNA水平与患者临床变量之间的相关性。VLDLR mRNA的水平在药物初治的精神分裂症患者，未用药的显着低于对照组。相比之下，药物初治患者的ApoER 2 mRNA水平与对照组无差异，尽管药物治疗患者的ApoER 2 mRNA水平显著低于对照组。有趣的是，药物初治患者的VLDLR mRNA水平在抗精神病药物治疗6个月后相对于基线显著增加，而ApoER 2 mRNA水平在治疗6个月后显著低于基线。在所有患者中，VLDLR mRNA水平与临床症状的严重程度呈负相关。我们的研究结果表明，外周VLDLR mRNA水平可能作为一个可靠的外周生物学标志物的精神分裂症，和reelin-VLDLR/ApoER 2信号通路在精神分裂症的病理生理中发挥作用。(C)2007 Elsevier B. V.保留所有权利。
Reelin, a secretory protease that plays major roles in neurodevelopment and synaptic plasticity, may also play a role in the pathogenesis of schizophrenia. The present study was undertaken to examine whether the expression of two receptors for reelin, very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor type 2 (ApoER2), were abnormal in peripheral blood lymphocytes of schizophrenic patients. In this study, we measured the mRNA levels of V-LDLR and ApoER2 in blood lymphocytes from patients with schizophrenia (drug-naive patients (n = 20) and medicated patients (n = 20)) and age-and gender-matched healthy controls (n = 40) using quantitative real-time RT-PCR. Furthermore, we examined the correlation between mRNA levels and clinical variables in patients. Levels of VLDLR mRNA in drug-naive, unmedicated patients with schizophrenia were significantly lower than those of controls. In contrast, levels of ApoER2 mRNA in drug-naive patients did not differ from those of controls, although the levels of ApoER2 mRNA in medicated patients were significantly lower than those of controls. Interestingly, levels of VLDLR mRNA in drug-naive patients showed significant increases with respect to baseline after six months of antipsychotic treatment, whereas levels of ApoER2 mRNA were significantly lower than baseline after six months of treatment. In all patients, there was a negative correlation between VLDLR mRNA levels and the severity of clinical symptoms. Our findings suggest that peripheral VLDLR mRNA levels may serve as a reliable peripheral biological marker of schizophrenia, and that the reelin-VLDLR/ApoER2 signaling pathway plays a role in the pathophysiology of schizophrenia. (C) 2007 Elsevier B.V. All rights reserved.