Fatemi S H, Kroll J L, Stary J M
Division of Neuroscience Research, Department of Psychiatry, University of Minnesota Medical School, Box 392, Mayo Building, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Neuroreport. 2001 Oct 29;12(15):3209-15. doi: 10.1097/00001756-200110290-00014.
Reelin is a secreted extracellular matrix protein approximately 410 kDa mol. wt that is reduced in brains of patients with schizophrenia, autism, bipolar disorder and major depression. Recent reports also indicate its near absence in sera of some patients with an autosomal recessive form of lissencephaly. Moreover, Reelin is involved not only in normal cortical lamination of the brain during mammalian embryogenesis but is also implicated in cell signaling systems subserving cognition in adult brain. Here, we show that blood levels of Reelin and its isoforms are altered in three psychiatric disorders, namely, schizophrenia, bipolar disorder and major depression. The changes include significant increases in 410 kDa Reelin moiety of 49% in schizophrenic patients (p < 0.022) of four ethnic compositions (Caucasian, Vietnamese, Hmong and Laotian) and non-significant increases in depressed patients by 34% vs control blood. In contrast, 410 kDa Reelin levels decreased by 33% in bipolar blood, albeit non-signficantly, vs. controls. There was a significant increase of 90% (p < 0.0061) in 330 kDa Reelin in Caucasian schizophrenics; the depressed value was elevated by 30% vs. control but non-significantly. Again, in contrast, bipolar 330 kDa value decreased by 31% vs control (p < 0.0480). Finally, all 180 kDa Reelin values varied minimally in schizophrenics vs controls. In contrast, the 180 kDa Reelin values dropped significantly by 49% (p < 0.0117) and 29% (p < 0.0424) in bipolar and depressed patients, respectively, compared with controls. The alterations in blood Reelin values appear to be specific since levels of two other blood proteins, ceruloplasmin and albumin did not vary significantly between all psychiatric subjects and controls. These findings suggest that blood Reelin levels and its isoforms may be used as potential peripheral markers to diagnose presence of several psychiatric disorders and may also serve as targets for future therapeutic interventions.
Reelin是一种分泌型细胞外基质蛋白，分子量约为410 kDa，在精神分裂症、自闭症、双相情感障碍和重度抑郁症患者的大脑中含量降低。最近的报告还表明，在一些患有常染色体隐性无脑回畸形的患者血清中几乎检测不到它。此外，Reelin不仅参与哺乳动物胚胎发育过程中大脑正常的皮质分层，还与成人大脑中支持认知的细胞信号系统有关。在此，我们表明，在三种精神疾病中，即精神分裂症、双相情感障碍和重度抑郁症，Reelin及其异构体的血液水平发生了改变。这些变化包括：在四种族组成（白种人、越南人、苗族和老挝人）的精神分裂症患者中，410 kDa的Reelin部分显著增加了49%（p < 0.022），而抑郁症患者相对于对照血液增加了34%，但不显著。相比之下，双相情感障碍患者血液中的410 kDa Reelin水平相对于对照组下降了33%，尽管不显著。在白种人精神分裂症患者中，330 kDa的Reelin显著增加了90%（p < 0.0061）；抑郁症患者的值相对于对照升高了30%，但不显著。同样，相比之下，双相情感障碍患者的330 kDa值相对于对照下降了31%（p < 0.0480）。最后，精神分裂症患者与对照组相比，所有180 kDa的Reelin值变化最小。相比之下，双相情感障碍患者和抑郁症患者的180 kDa Reelin值分别比对照组显著下降了49%（p < 0.0117）和29%（p < 0.0424）。血液中Reelin值的改变似乎具有特异性，因为另外两种血液蛋白，即铜蓝蛋白和白蛋白的水平在所有精神疾病受试者和对照组之间没有显著差异。这些发现表明，血液中Reelin水平及其异构体可能用作诊断几种精神疾病存在的潜在外周标志物，也可能成为未来治疗干预的靶点。
