Smoking and schizophrenia: abnormal nicotinic receptor expression
Smoking and schizophrenia: abnormal nicotinic receptor expression
复制标题
DOI：
10.1016/s0014-2999(00)00035-2
复制
发表时间：
2000-03-30
影响因子：
5
通讯作者：
Freedman, R
中科院分区：
文献类型：
--
作者：
Leonard, S;Breese, C;Freedman, R
生物学和遗传学证据表明神经元烟碱受体在精神分裂症的神经病理生理中起作用。尼古丁使患有此病的人的听觉诱发电位缺陷正常化。与对照组相比，精神分裂症患者死后脑中具有高亲和力和低亲和力的尼古丁受体均减少。人类α -7基因的染色体位点（15q14）与门控缺陷相关，其lod为5.3，α -7受体的拮抗剂（α -bungarotoxin和甲基莱卡乌碱）可诱导啮齿动物的门控丧失。我们克隆了人类α -7基因，发现它在全长基因的近端部分复制。这种复制在正常人的大脑和外周血细胞中都有表达，但在一些精神分裂症患者中却没有。这些研究结果提示神经烟碱受体基因家族在精神分裂症中存在异常的表达和功能。(C) 2000 Elsevier Science B.V.版权所有
Biological and genetic evidence suggests a role for the neuronal nicotinic receptors in the neuropathophysiology of schizophrenia. Nicotine normalizes an auditory evoked potential deficit seen in subjects who suffer from the disease. Nicotinic receptors with both high and low affinity for nicotine are decreased in postmortem brain of schizophrenics compared to control subjects. The chromosomal locus of the human alpha-7 gene (15q14) is linked to the gating deficit with a lod of 5.3, and antagonists of the alpha-7 receptor (alpha-bungarotoxin and methyllycaconitine) induce a loss of gating in rodents. We have cloned the human alpha-7 gene and found it to be partially duplicated proximal to the full-length gene. The duplication is expressed in both the brain and in peripheral blood cells of normal subjects, but is missing in some schizophrenic subjects. The results of these studies suggest the presence of abnormal expression and function of the neuronal nicotinic receptor gene family in schizophrenia. (C) 2000 Elsevier Science B.V. All rights reserved.