Simpson M D, Royston M C, Deakin J F, Cross A J, Mann D M, Slater P
Department of Physiological Sciences, University of Manchester, U.K.
Brain Res. 1988 Oct 11;462(1):76-82. doi: 10.1016/0006-8993(88)90587-2.
The specific binding of [3H]D-aspartate, a marker for the presynaptic glutamate uptake site, and [3H]N-(1-[2-Thienyl]cyclohexyl)-piperidine [( 3H]TCP), a high affinity ligand for the N-methyl-D-aspartate (NMDA)-associated phencyclidine binding site, was measured in homogenates of brain from normal subjects and from subjects with neuropathologically confirmed Alzheimer's disease. Alzheimer's disease was associated with a reduction in [3H]D-aspartate binding density in temporal cortex and caudate nucleus. By contrast, a reduction in the receptor density for [3H]TCP binding was only recorded in the frontal cortex. Thus, glutamate-containing nerve terminals are severely reduced in Alzheimer's disease, whilst the postsynaptic NMDA-phencyclidine receptor complex is much less affected. These findings have implications for theories of glutamate neurotoxicity in Alzheimer's disease.
[3H]D-天冬氨酸是突触前谷氨酸摄取位点的标志物，[3H]N-(1-[2-噻吩基]环己基)-哌啶([3H]TCP)是与N-甲基-D-天冬氨酸(NMDA)相关的苯环己哌啶结合位点的高亲和力配体，对正常受试者和经神经病理学证实为阿尔茨海默病的受试者的脑匀浆进行了特异性结合测定。阿尔茨海默病与颞叶皮质和尾状核中[3H]D-天冬氨酸结合密度降低有关。相比之下，仅在额叶皮质记录到[3H]TCP结合的受体密度降低。因此，在阿尔茨海默病中，含谷氨酸的神经末梢严重减少，而突触后NMDA-苯环己哌啶受体复合物受影响较小。这些发现对阿尔茨海默病中谷氨酸神经毒性理论具有重要意义。
