NMDA, AMPA, AND BENZODIAZEPINE BINDING-SITE CHANGES IN ALZHEIMERS-DISEASE VISUAL-CORTEX
NMDA, AMPA, AND BENZODIAZEPINE BINDING-SITE CHANGES IN ALZHEIMERS-DISEASE VISUAL-CORTEX
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DOI：
10.1016/0197-4580(93)90120-z
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发表时间：
1993-07-01
影响因子：
4.2
通讯作者：
YOUNG, AB
中科院分区：
文献类型：
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作者：
CARLSON, MD;PENNEY, JB;YOUNG, AB
定量受体放射自显影用于测量[H-3]甘氨酸和[H-3]谷氨酸与N-甲基-D-天冬氨酸（NMDA）受体复合物的结合，[H-3]D，L-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）与AMPA受体的结合，和[H-3]氟硝西泮与对照和阿尔茨海默病（AD）死后人脑视皮层三个区域中苯二氮卓（BDZ）受体的结合（初级或条纹状视觉皮层、视觉关联皮层和高级视觉关联皮层，分别对应于布罗德曼区域17、18和21）。在区域17中，AD脑中与NMDA、AMPA和BDZ受体的结合没有显著改变（除了在[H-3]甘氨酸的第VI层和[H-3]AMPA的第III层中，AD脑中的结合减少）。然而，与区域18中的两种EAA受体结合的配体在AD脑中显著减少（对于[H-3]甘氨酸，层I至III，对于[H-3]AMPA，层III至VI）。在区域2 - 1中，与NMDA和BDZ受体结合但不与AMPA受体结合，在AD脑的几乎所有层中均显著降低（[H-3]甘氨酸的I至VI层和[H-3]氟硝西泮的I至V层）。这种分层模式的层状结合损失与关联视觉皮层的复杂性增加是一致的，在这些领域发现的神经元缠结的数量增加，涉及NMDA和BDZ受体轴承细胞在AD神经病理学。AMPA受体损失不平行的病理，表明AMPA受体与病理没有直接相关。
Quantitative receptor autoradiography was used to measure the laminar distribution of [H-3]glycine and [H-3]glutamate binding to the N-methyl-D-aspartate (NMDA) receptor complex, [H-3]D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) binding to the AMPA receptor, and [H-3]flunitrazepam binding to the benzodiazepine (BDZ) receptor in three areas of visual cortex in control and Alzheimer's disease (AD) postmortem human brains (primary or striate visual cortex, visual association cortex, and higher-order visual association cortex, corresponding to Brodmann Areas 17, 18, and 21, respectively). In Area 17, binding to the NMDA, AMPA, and BDZ receptors was not significantly altered in the AD brains (except in layer VI for [H-3]glycine and layer III for [H-3]AMPA, where binding was reduced in the AD brains). Ligand binding to the two EAA receptors in Area 18 was, however, significantly reduced in the AD brains (layers I through III for [H-3]glycine and layers III through VI for [H-3]AMPA). In Area 2 1, binding to both the NMDA and BDZ receptors but not to the AMPA receptor, was significantly reduced in almost all laminae of the AD brains (layers I through VI for [H-3]glycine and layers I through V for [H-3]flunitrazepam). This hierarchical pattern of laminar binding loss with increasing complexity of association visual cortices is consistent with the increasing numbers of neurofibrillary tangles found in those areas, implicating NMDA and BDZ receptor bearing cells in AD neuropathology. AMPA receptor losses do not parallel the pathology, suggesting that AMPA receptors are not directly correlated with the pathology.