β-Amyloid-related peptides potentiate K+-evoked glutamate release from adult rat hippocampal slices
β-Amyloid-related peptides potentiate K+-evoked glutamate release from adult rat hippocampal slices
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DOI：
10.1016/j.neurobiolaging.2008.08.009
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发表时间：
2010-07-01
影响因子：
4.2
通讯作者：
Kar, S.
中科院分区：
文献类型：
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作者：
Kabogo, D.;Rauw, G.;Kar, S.
积累的证据表明，β 淀粉样蛋白 (Aβ) 肽通过与中枢谷氨酸能系统相互作用，可导致与阿尔茨海默病 (AD) 病理相关的神经元变性。然而，目前对于 Aβ 肽在正常大脑谷氨酸功能调节中的作用知之甚少。鉴于 A β 肽在正常大脑中组成型产生的证据，我们研究了含有淀粉样前体蛋白 (APP) 的神经元与囊泡谷氨酸转运蛋白 1 (VGIuT1) 的可能关联，并测量了各种 A β 肽对成年大鼠脑切片内源性谷氨酸释放的影响。我们的结果表明，VGIuTI 免疫反应性位于与 APP 神经元紧密相连的位置，并且外源性 A beta(1-40) 以剂量依赖性（10(-12) 至 10(-7) M）方式有效增加 K+ 诱发的海马切片谷氨酸释放。其他 A β 肽如 A β(1-42)、A β(1-28) 和 A β(25-35) 也观察到了这种效应，但反向 A β(1-40) 或 A β(25-35) 序列则没有观察到这种效应。河豚毒素未能改变 A beta(1-40) 对谷氨酸释放的影响，这表明缺乏电压依赖性 Na+ 通道的参与。除了海马体之外，A beta(1-40) 还被发现可以增强皮质切片中 K+ 诱发的谷氨酸释放，而在纹状体中，这种效果并未达到显着水平。这些结果表明，Aβ肽的生理浓度可以通过作用于谷氨酸能末端来调节谷氨酸的释放。此外，有证据表明大脑的某些区域对 Aβ 肽敏感，这表明 Aβ 的沉积与 AD 病理学中观察到的大脑区域的优先脆弱性之间存在潜在联系。 (C) 2008 Elsevier Inc. 保留所有权利。
Accumulated evidence indicates that amyloid beta (A beta) peptides, by interacting with the central glutamatergic system, can lead to degeneration of neurons associated with Alzheimer's disease (AD) pathology. However, very little is currently known about the role of A beta peptides in the regulation of glutamatergic function in the normal brain. Given the evidence that A beta peptides are produced constitutively in the normal brain, we investigated the possible association of amyloid precursor protein (APP)-containing neurons with the vesicular glutamatergic transporter-1 (VGIuT1) and measured the effects of various A beta peptides on endogenous glutamate release from adult rat brain slices. Our results showed that VGIuTI immunoreactivity is localized in close apposition to APP neurons, and that exogenous A beta(1-40), in a dose-dependent (10(-12) to 10(-7) M) manner potently increased K+-evoked glutamate release from hippocampal slices. This effect was observed with other A beta peptides such as A beta(1-42), A beta(1-28) and A beta(25-35), but not with the reverse A beta(1-40) or A beta(25-35) sequences. Tetrodotoxin failed to alter the effects of A beta(1-40) on glutamate release, which suggests the lack of involvement of voltage-dependent Na+ channels. In addition to the hippocampus, A beta(1-40) was found to potentiate K+-evoked glutamate release from cortical slices, whereas in the striatum the effect did not reach significant levels. These results demonstrate that physiological concentrations of A beta peptides can regulate the release of glutamate by acting on glutamatergic terminals. Additionally, the evidence that selected regions of the brain are sensitive to A beta peptides suggests a potential link between the deposition of A beta and the preferential vulnerability of brain regions observed in AD pathology. (C) 2008 Elsevier Inc. All rights reserved.