CIRCULATING REELIN AND PSYCHOSIS VULNERABILITY

描述：（改编自申请人的摘要）缫丝是一个大的分泌 在层状结构的形成中起关键作用的糖蛋白 在大脑中也有表达，在成人大脑中也有表达。Reelin 在死后的多个区域， 精神分裂症和躁郁症患者的大脑。Reeler杂合子 突变小鼠，其在大脑中表达的reelin为野生型的50 水平，表现出离散的神经解剖和行为异常，包括 对惊吓的前脉冲抑制丧失，这是精神病的特征。 这些研究结果表明，在规模上类似的reelin赤字， 在精神病中会影响正常脑功能， 精神病患者可能先于他们的疾病，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是表达在 血清和血浆中的小鼠，大鼠和人类，这提高了令人兴奋的 即使在活着的人类中也可能检测到reelin异常， 在症状出现之前，允许一个人遵循早期过程， 精神病和开始早期干预。为了评估 测量循环中的reelin水平作为精神分裂症的指标 脆弱性，研究人员建议：1。建立定量 竞争性RIA测定血浆中的reelin。和2.提高单克隆 识别reelin的中间和C末端结构域的抗体。 这些研究不仅将为研究患有糖尿病的人群奠定基础， (or精神分裂症的风险，但将有更广泛的影响， 研究测量CSF和循环回线的潜在效用， 其他神经和精神疾病，以及基础问题 关于外周中的reelin的生理作用。

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.