Biochemical and molecular studies of NMDA receptor subunits NR1/2A/2B in hippocampal subregions throughout progression of Alzheimer's disease pathology
Biochemical and molecular studies of NMDA receptor subunits NR1/2A/2B in hippocampal subregions throughout progression of Alzheimer's disease pathology
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DOI：
10.1016/j.nbd.2003.09.016
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发表时间：
2004-02-01
影响因子：
6.1
通讯作者：
Armstrong, DM
中科院分区：
文献类型：
--
作者：
Mishizen-Eberz, AJ;Rissman, RA;Armstrong, DM
阿尔茨海默病（AD）的特点是海马的选择性亚区中特定细胞群的丧失。通过嗜离子性谷氨酸受体介导的兴奋性毒性可能在这种选择性神经元易感性中起关键作用。我们研究了NMDA受体亚基在AD进展过程中是否发生改变。采用生物化学和原位杂交技术，对各种AD病理对象进行蛋白水平和NR1/2A/2B亚基mRNA表达的检测。随着AD神经病理程度的增加，NR1/2B亚基的蛋白水平和mRNA表达量显著降低，而NR2A亚基mRNA表达和蛋白水平不变。神经元mRNA表达的细胞分析显示，中度神经原纤维缠结神经病理受试者的NR2A亚基显著增加。该研究支持了一种假设，即随着AD病理严重程度的增加，特定NMDA受体亚基的表达会发生改变，这可能导致这些神经元的易感性。(C) 2003 Elsevier Inc.版权所有。
Alzheimer's disease (AD) is characterized by loss of specific cell populations within selective subregions of the hippocampus. Excitotoxicity, mediated via ionotropic glutamate receptors, may play a crucial role in this selective neuronal vulnerability. We investigated whether alterations in NMDA receptor subunits occurred during AD progression. Employing biochemical and in situ hybridization techniques in subjects with a broad range of AD pathology, protein levels, and mRNA expression of NR1/2A/2B subunits were assayed. With increasing AD neuropathology, protein levels and mRNA expression for NR1/2B subunits were significantly reduced, while the NR2A subunit mRNA expression and protein levels were unchanged. Cellular analysis of neuronal mRNA expression revealed a significant increase in the NR2A subunit in subjects with moderate neurofibrillary tangle neuropathology. This investigation supports the hypothesis that alterations occur in the expression of specific NMDA receptor subunits with increasing AD pathologic severity, which is hypothesized to contribute to the vulnerability of these neurons. (C) 2003 Elsevier Inc. All rights reserved.