GLUTAMATE-RECEPTOR SUBTYPE EXPRESSION IN HUMAN POSTMORTEM BRAIN-TISSUE FROM SCHIZOPHRENICS AND ALCOHOL ABUSERS
GLUTAMATE-RECEPTOR SUBTYPE EXPRESSION IN HUMAN POSTMORTEM BRAIN-TISSUE FROM SCHIZOPHRENICS AND ALCOHOL ABUSERS
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DOI：
10.1016/0006-8993(94)01384-t
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发表时间：
1995-03-13
期刊：
影响因子：
2.9
通讯作者：
LEONARD, SS
中科院分区：
文献类型：
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作者：
BREESE, CR;FREEDMAN, R;LEONARD, SS
功能AMPA/红藻氨酸（GluR 1，GluR 2，GluR 3）和红藻氨酸结合位点（GluR 5 -7）的抗体被用作探针来表征和定量精神分裂症受试者和非精神病对照受试者（包括正常对照和既往有酗酒史的受试者）的人死后脑组织中的谷氨酸能受体亚型。粗膜馏分从人类大脑皮层和扣带皮层的SDS-PAGE分级，电转移到硝酸纤维素，并探测各种谷氨酸受体亚型。免疫印迹用化学发光显色，并通过光密度法分析图像。与整个非精神病对照组相比，精神分裂症受试者中GluR 2和GluR 3 AMPA/红藻氨酸受体亚型的海马免疫反应性显著降低。在精神分裂症海马GluR 1和GluR 5受体亚型或结构控制蛋白NCAM和tau水平中未观察到显著变化。与非精神病正常对照组相比，在有酒精滥用史的受试者的大脑皮层中观察到GluR 2和GluR 3显著增加。当从非精神病对照组中排除有酗酒史的受试者时，精神分裂症患者与其余正常对照组之间不再存在统计学差异。GluR 2和GluR 3在扣带皮层的免疫反应性分析显示，这些受体亚型之间的任何组没有变化。由于年龄、性别、死后间隔或吸烟史等混杂因素，这些不同蛋白质的免疫反应性没有观察到改变，但吸烟者大脑中扣带回皮质中GluR 3受体亚型水平显著降低。这些结果通常不支持精神分裂症中的非NMDA型谷氨酸能受体的作用。然而，慢性乙醇暴露对人类大脑的作用需要进一步研究，并强调了人类死后研究中确定对照组织的重要性。
Antibodies to functional AMPA/kainate (GluR1, GluR2, GluR3), and kainate binding sites (GluR5-7) were used as probes to characterize and quantitate glutamatergic receptor subtypes in human post-mortem brain tissue from schizophrenic subjects and non-psychotic control subjects, which included normal controls and subjects with a previous history of alcohol abuse. Crude membrane fractions from human hippocampi and cingulate cortices were fractionated by SDS-PAGE, electrotransferred to nitrocellulose, and probed for the various glutamate receptor subtypes. Western blots were developed with chemiluminescence and the images analyzed by densitometry. Significant reductions were observed in the hippocampal immunoreactivity of both GluR2 and GluR3 AMPA/kainate receptor subtypes in schizophrenic subjects compared to the entire group of non-psychotic control subjects. No significant changes were observed in schizophrenic hippocampal GluR1 and GluR5 receptor subtypes or in levels of the structural control proteins, NCAM and tau. Significant increases were observed for GluR2 and GluR3 in the hippocampi of subjects with alcohol abuse histories when compared to the non-psychotic normal control group. When subjects with alcohol abuse histories were removed from the non-psychotic control pool, schizophrenics were no longer statistically different from the remaining normal controls. An analysis of GluR2 and GluR3 immunoreactivity in the cingulate cortex revealed no changes in these receptor subtypes among any of the groups. No alterations were observed in the immunoreactivity of these various proteins due to confounding factors such as age, sex, postmortem interval, or smoking history, except in the cingulate cortex were GluR3 receptor subtype levels were significantly reduced in the brains of smokers. These results generally do not support a role for the non-NMDA type glutamatergic receptors in schizophrenia. However, the role of chronic ethanol exposure on the human brain needs to be further investigated, and underscores the importance of defined control tissue for human postmortem studies.