CIRCULATING REELIN AND PSYCHOSIS VULNERABILITY

描述：(改编自申请者的摘要)Reelin是一个大秘密 糖蛋白在层状结构发育中的关键作用 在大脑中，它也在成年人的大脑中表达。收卷 在死后的多个区域中，表达减少了约50% 精神分裂症和双相情感障碍患者的大脑。绞线虫杂合子 突变小鼠，它们在大脑中表达卷轴蛋白的比例是野生型的50% 水平，表现出离散的神经解剖和行为异常，包括 失去对惊吓的脉冲前抑制，这是精神病的一个特征。 这些发现表明，卷轴赤字的规模与之前看到的类似 精神错乱会影响正常的大脑功能，而在 精神病患者可能先于他们的疾病，并使他们的大脑更容易受到 导致精神病的致病因素。 研究人员最近发现，reelin在 小鼠、大鼠和人类的血清和血浆，这提高了兴奋性 甚至在活人身上也可能检测到卷轴异常 在症状出现之前，允许一个人遵循早期的病程 并开始早期干预。为了评估其价值 检测血液循环卷轴蛋白水平作为精神分裂症的指标 对于脆弱性，调查人员建议：1.建立一个定量的 竞争放射免疫法测定血浆中的卷曲蛋白。2.培育单抗 识别reelin的中间和C末端结构域的抗体。 这些研究不仅将为人类种群的研究奠定基础 精神分裂症(或有精神分裂症的风险)，但将对 脑脊液和循环卷叶蛋白测定的临床应用探讨 其他神经和精神疾病，以及基础问题 关于卷轴在外周的生理作用(S)。

DESCRIPTION: (Adapted from applicant's abstract) Reelin is a large secreted glycoprotein which plays a critical role in development of laminated structures within the brain, and which is expressed in adult brain as well. Reelin expression is decreased about50 percent in multiple regions of post-mortem brains of patients with schizophrenia and bipolar illness. Reeler heterozygous mutant mice, which express reelin within the brain at 50 percent of wild-type levels, exhibit discrete neuroanatomical and behavioral abnormalities including loss of prepulse inhibition of startle, a trait characteristic of psychosis. These findings suggest that reelin deficits similar in magnitude to those seen in psychosis can affect normal brain function, and that reelin abnormalities in psychotics may precede their illness and render their brains more vulnerable to pathogenetic factors that cause psychosis. The investigators have recently discovered that reelin is expressed in the serum and plasma in mice, rats and humans, which raises the exciting possibility that reelin abnormalities may be detectable in living humans even prior to the onset of symptoms, allowing one to follow the early course of psychosis and to begin early interventions. In order to assess the value of measuring circulating reelin levels as an indicator of schizophrenic vulnerability, the investigators propose to: 1. Establish a quantitative competitive RIA for measuring reelin in plasma. And 2. Raise monoclonal antibodies that recognize the mid- and C-terminal domains of reelin. These studies will not only set the stage for studies of human populations with (or at risk of) schizophrenia, but will have broader implications for investigating the potential utility of measuring CSF and circulating reelin in other neurological and psychiatric diseases, as well as for base issues regarding the physiologic role(s) of reelin in the periphery.