Soluble oligomers of β amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus
Soluble oligomers of β amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus
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DOI：
10.1016/s0006-8993(01)03058-x
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发表时间：
2002-01-11
期刊：
影响因子：
2.9
通讯作者：
Trommer, BL
中科院分区：
文献类型：
--
作者：
Wang, HW;Pasternak, JF;Trommer, BL
阿尔茨海默病（Alzheimer disease，AD）的痴呆通常归因于广泛的神经元损失以及细胞内神经元缠结和含有纤维状淀粉样蛋白（A β）的细胞外斑块的病理特征。最近已经证明，Abeta的非纤维组装体具有电生理活性，其推论是它们可能通过在细胞死亡之前破坏神经元信号传导而产生痴呆。因此，我们在大鼠海马切片的齿状回中检测了Abeta的可溶性寡聚体（1.42）对长时程增强（LTP）和长时程抑制（LTD）（两种记忆的细胞模型）的影响。与媒介物对照相比，在A β衍生的可扩散配体（ADDL）存在下预孵育60分钟的切片在引起突触反应的阈值强度方面没有差异。场兴奋性突触后电位（EPSP）的斜率，或输入/输出函数。破伤风诱导的LTP和逆转的LTD强烈抑制ADDL处理的切片，而LTD不受影响。这些数据表明，可溶性非纤维状淀粉样蛋白可能有助于AD的发病机制，既通过损害LTP/记忆形成在细胞水平上，并通过创建'神经可塑性失衡'表现为unopposed LTD在设置受损的能力，通过逆转LTD或LTP的神经修复。(C)2002 Elsevier Science B. V.保留所有权利。
The dementia in Alzheimer disease (AD) is usually attributed to widespread neuronal loss in conjunction with the pathologic hallmarks of intracellular neurofibrillary tangles and extracellular plaques containing amyloid (Abeta) in fibrillar form. Recently it has been demonstrated that non-fibrillar assemblies of Abeta possess electrophysiologic activity, with the corollary that they may produce dementia by disrupting neuronal signaling prior to cell death, We therefore examined the effects of soluble oligomers of Abeta(1.42) on long-term potentiation (LTP) and long-term depression (LTD), two cellular models of memory, in the dentate gyrus of rat hippocampal slices. Compared with vehicle controls, slices pre-incubated 60 min in the presence of Abeta-derived diffusible ligands (ADDLs) showed no differences in threshold intensity to evoke a synaptic response. slope of field excitatory post-synaptic potentials (EPSPs), or the input/output function. Tetanus-induced LTP and reversal of LTD were strongly inhibited in ADDLs-treated slices whereas LTD was unaffected. These data suggest that soluble non-fibrillar amyloid may contribute to the pathogenesis of AD both by impairing LTP/memory formation at the cellular level and by creating 'neuroplasticity imbalance' manifested by unopposed LTD in the setting of impaired capacity for neural repair via reversal of LTD or LTP. (C) 2002 Elsevier Science B.V. All rights reserved.