Excitatory amino acid binding sites in the hippocampal region of Alzheimer's disease and other dementias.
Excitatory amino acid binding sites in the hippocampal region of Alzheimer's disease and other dementias.
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阿尔茨海默病和其他痴呆症海马区的兴奋性氨基酸结合位点。
DOI：
10.1136/jnnp.53.4.314
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Young,AB
中科院分区：
文献类型：
--
作者：
Penney,JB;Maragos,WF;Greenamyre,JT;Debowey,DL;Hollingsworth,Z;Young,AB
使用定量受体放射自显影技术测量 10 名阿尔茨海默病患者海马区邻近切片中毒蕈碱胆碱能、苯二氮卓类、红藻氨酸、苯环己哌啶 (PCP)、N-甲基-D-天冬氨酸 (NMDA)（在 Tris 乙酸盐中测量）、君子氨酸敏感、非君子氨酸敏感和总谷氨酸（在 Tris 氯化物缓冲液中测量）结合位点，九个对照者和六个精神错乱的、非阿尔茨海默氏病的死后人类大脑。将测量结果与相邻切片的刚果红染色显示的神经原纤维缠结的数量进行比较。所有分析和测量均由对临床诊断不知情的观察者完成。在阿尔茨海默病大脑的 CA1 锥体层中，除君子氨酸外，所有配体的结合均显着降低。非使君子酸和 NMDA 位点的结合损失明显大于毒蕈碱、苯二氮卓和红藻氨酸位点的结合损失，总谷氨酸和 PCP 位点损失处于中等水平。只有苯二氮卓结合的丧失与神经原纤维缠结的数量显着相关。在邻近区域观察到较少的结合损失。这种结合减少程度的差异与 NMDA 受体位于海马神经元更远端树突上的假设一致。在那里，它们可能比其他受体更容易受到病理过程的影响。
Quantitative receptor autoradiography was used to measure muscarinic cholinergic, benzodiazepine, kainate, phencyclidine (PCP), N-methyl-D-aspartate (NMDA) (measured in Tris acetate), quisqualate-sensitive, non-quisqualate-sensitive and total glutamate (measured in Tris chloride buffer) binding sites in adjacent sections of the hippocampal region of 10 Alzheimer's disease, nine control, and six demented, non-Alzheimer's disease postmortem human brains. The measurements were compared to the number of neurofibrillary tangles as revealed by Congo red staining of adjacent sections. All assays and measurements were done by observers blinded to the clinical diagnoses. Binding was decreased significantly for all ligands except quisqualate in stratum pyramidale of CA1 of the Alzheimer's disease brains. The binding loss was significantly greater for the non-quisqualate and NMDA sites than for the muscarinic, benzodiazepine and kainate sites with the total glutamate and PCP site losses being intermediate. Only the loss of benzodiazepine binding was significantly correlated with the number of neurofibrillary tangles. Lesser binding losses were seen in adjacent areas. This difference in the degree of binding decrease is consistent with the hypothesis that NMDA receptors are located on more distal dendrites of hippocampal neurons. There they may be relatively more vulnerable than the other receptors to the pathological process.