GLUTAMATE METABOTROPIC AND AMPA BINDING-SITES ARE REDUCED IN ALZHEIMERS-DISEASE - AN AUTORADIOGRAPHIC STUDY OF THE HIPPOCAMPUS
GLUTAMATE METABOTROPIC AND AMPA BINDING-SITES ARE REDUCED IN ALZHEIMERS-DISEASE - AN AUTORADIOGRAPHIC STUDY OF THE HIPPOCAMPUS
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DOI：
10.1016/0006-8993(91)90230-s
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发表时间：
1991-07-05
期刊：
影响因子：
2.9
通讯作者：
MCCULLOCH, J
中科院分区：
文献类型：
--
作者：
DEWAR, D;CHALMERS, DT;MCCULLOCH, J
应用定量放射自显影技术研究了正常人和阿尔茨海默病患者海马区谷氨酸代谢型结合位点的分布和水平。谷氨酸代谢型结合位点的地形进行了对比，红藻氨酸和2-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）在相邻的切片从相同的主题。谷氨酸代谢型结合和AMPA结合的区域分布相似，在海马下托和CA 1区最丰富，在CA 3区较低。红藻氨酸结合的分布不同于代谢型结合，在海马旁回和CA 3的深层中最大，在下托和CA 1中较低。在阿尔茨海默病患者中，这些非N-甲基-D-天冬氨酸（非NMDA）结合位点存在区域性明显减少。谷氨酸代谢型，AMPA和红藻氨酸结合各自显着减少下托和下托内的神经元损失相关的变化幅度。谷氨酸代谢型结合和AMPA结合显着减少在CA 1阿尔茨海默氏病的受试者，而红藻氨酸结合在这一地区的最低限度的改变。在阿尔茨海默病患者海马旁回，红藻氨酸和AMPA结合显著减少，而谷氨酸代谢型结合则没有。在许多海马区（例如齿状回，CA 3），所有配体的结合在阿尔茨海默病中改变最小。这些差异可能反映了神经元元件上的三种类型的谷氨酸结合位点的本地化，这些神经元元件对阿尔茨海默病的神经退行性过程具有差异敏感性。
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.