β-amyloid peptide activates non-α7 nicotinic acetylcholine receptors in rat basal forebrain neurons
β-amyloid peptide activates non-α7 nicotinic acetylcholine receptors in rat basal forebrain neurons
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DOI：
10.1152/jn.00616.2003
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发表时间：
2003-11-01
影响因子：
2.5
通讯作者：
Jhamandas, JH
中科院分区：
文献类型：
--
作者：
Fu, W;Jhamandas, JH
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征在于记忆和认知功能的严重缺陷。该疾病的神经病理学特征包括基底前脑胆碱能神经元的损失和β-淀粉样肽（Abeta）在神经炎斑块中的沉积。在细胞水平上，相当多的注意力集中在与神经元烟碱乙酰胆碱受体（nAChR）亚型的Abeta相互作用的研究。在这项研究中，使用急性分离的大鼠基底前脑神经元的细胞贴附和外向单通道记录，我们报告说，Abeta和尼古丁激活nAChRs与两个不同水平的单通道电导。来自这些神经元的全细胞记录显示Abeta和尼古丁以浓度依赖性和可逆的方式引起快速去极化反应和内向电流。非竞争性nAChR拮抗剂美加明和竞争性nAChR拮抗剂dihydro-beta-erythroidine可阻断Abeta对单通道和全细胞的作用，但特异性α 7选择性nAChR拮抗剂甲基甘草次酸不能阻断，表明Abeta激活基底前脑神经元上的非α 7 nAChR。此外，非α 7 nAChR激动剂UB-165、地棘蛙素和野靛碱（而非选择性α 7激动剂AR-R17779）诱导的反应与Abeta和尼古丁相似。因此，非α 7 nAChR也可能是介导AD中Abeta作用的新靶点。
Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by profound deficits in memory and cognitive function. Neuropathological hallmarks of the disease include a loss of basal forebrain cholinergic neurons and the deposition of beta-amyloid peptide (Abeta) in neuritic plaques. At a cellular level, considerable attention has focused on a study of Abeta interactions with the neuronal nicotinic acetylcholine receptor (nAChR) subtypes. In this study, using cell-attached and outside-out single channel recordings from acutely dissociated rat basal forebrain neurons, we report that Abeta and nicotine activate nAChRs with two distinct levels of single-channel conductance. Whole cell recordings from these neurons reveal Abeta and nicotine, in a concentration-dependent and reversible manner, evoke brisk depolarizing responses and an inward current. The effects of Abeta on both single channel and whole cell are blocked by the noncompetitive nAChR antagonist mecamylamine and competitive nAChR antagonist dihydro-beta-erythroidine, but not the specific alpha7-selective nAChR antagonist methyllycaconitine, indicating that Abeta activated non-alpha7 nAChRs on basal forebrain neurons. In addition, the non-alpha7 nAChR agonists UB-165, epibatidine, and cytisine, but not the selective alpha7 agonist AR-R17779, induced similar responses as Abeta and nicotine. Thus non-alpha7 nAChRs may also represent a novel target in mediating the effects of Abeta in AD.