Dewar D, Chalmers D T, Graham D I, McCulloch J
Wellcome Surgical Institute, University of Glasgow, U.K.
Brain Res. 1991 Jul 5;553(1):58-64. doi: 10.1016/0006-8993(91)90230-s.
The distribution and levels of glutamate metabotropic binding sites were investigated in the hippocampal region of the human brain using quantitative autoradiography in normal subjects and patients with Alzheimer's disease. The topography of glutamate metabotropic binding sites was contrasted with those for kainate and 2-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) in adjacent sections from the same subjects. The regional distribution of glutamate metabotropic binding and AMPA binding were similar, being most abundant in the subiculum and CA1 region and lower in the CA3 region. The distribution of kainate binding differed from that of metabotropic binding being greatest in the deep layers of the parahippocampal gyrus and CA3 and lower in the subiculum and CA1. There were regionally distinct reductions in these non-N-methyl-D-aspartate (non-NMDA) binding sites in patients with Alzheimer's disease. Glutamate metabotropic. AMPA and kainate binding were each markedly reduced in the subiculum and the magnitude of the change correlated with neuronal loss within the subiculum. Glutamate metabotropic binding and AMPA binding were reduced significantly in CA1 in subjects with Alzheimer's disease whereas kainate binding was minimally altered in this region. Kainate and AMPA binding were reduced significantly in the parahippocampal gyrus in Alzheimer's disease while glutamate metabotropic binding was not. In a number of hippocampal areas (e.g. dentate gyrus, CA3), the binding of all ligands was minimally altered in Alzheimer's disease. These differences may reflect the localisation of the three types of glutamate binding sites on neuronal elements which are differentially susceptible to the neurodegenerative process of Alzheimer's disease.
利用定量放射自显影技术，在正常受试者和阿尔茨海默病患者的人脑海马区研究了代谢型谷氨酸结合位点的分布和水平。将代谢型谷氨酸结合位点的拓扑结构与同一受试者相邻切片中的 kainate 和 2-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）结合位点的拓扑结构进行对比。代谢型谷氨酸结合和 AMPA 结合的区域分布相似，在海马下脚和 CA1 区最为丰富，在 CA3 区较低。kainate 结合的分布与代谢型结合不同，在海马旁回深层和 CA3 区最大，在海马下脚和 CA1 区较低。阿尔茨海默病患者这些非 N-甲基-D-天冬氨酸（非 NMDA）结合位点存在区域特异性减少。海马下脚中代谢型谷氨酸、AMPA 和 kainate 结合均显著降低，变化幅度与海马下脚内的神经元丢失相关。阿尔茨海默病患者 CA1 区代谢型谷氨酸结合和 AMPA 结合显著降低，而该区域 kainate 结合变化最小。阿尔茨海默病患者海马旁回中 kainate 和 AMPA 结合显著降低，而代谢型谷氨酸结合未降低。在一些海马区域（如齿状回、CA3），阿尔茨海默病患者所有配体的结合变化最小。这些差异可能反映了三种类型谷氨酸结合位点在神经元成分上的定位，这些神经元成分对阿尔茨海默病的神经退行性过程的易感性不同。
