Departamento de Farmacobiología, Cinvestav-Sede Sur, México, D.F., México.
Peptides. 2010 Sep;31(9):1761-6. doi: 10.1016/j.peptides.2010.06.003. Epub 2010 Jun 14.
Alzheimer disease (AD) patients show alterations in both neuronal network oscillations and the cognitive processes associated to them. Related to this clinical observation, it has been found that amyloid beta protein (Abeta) differentially affects some hippocampal network activities, reducing theta and gamma oscillations, without affecting sharp waves and ripples. Beta-like oscillations is another cognitive-related network activity that can be evoked in hippocampal slices by several experimental manipulations, including bath application of kainate and increasing extracellular potassium. Here, we tested whether or not different Abeta peptides differentially affect beta-like oscillatory patterns. We specifically tested the effects of fresh dissolved Abeta(25-35) and oligomerized Abeta(1-42) and found that kainate-induced oscillatory network activity was affected, in a slightly concentration dependent-manner, by both fresh dissolved (mostly monomeric) Abeta(25-35) and oligomeric Abeta(1-42). In contrast, potassium-induced oscillatory activity, which is reduced by oligomeric Abeta(1-42), is not affected by monomeric Abeta(25-35) at any of the concentrations tested. Our results support the idea that different amyloid peptides might alter specific cellular mechanisms related to the generation of specific neuronal network activities, instead of a generalized inhibitory effect of Abeta peptides on neuronal network function.
阿尔茨海默病(AD)患者的神经元网络活动及其相关认知过程均发生改变。基于这一临床观察,研究发现β淀粉样蛋白(Abeta)可特异性影响海马区的部分网络活动,降低θ波和γ波频率,但不影响棘波和锐波。β样振荡是另一种与认知相关的网络活动,可通过多种实验操作在海马切片中诱发,包括灌流应用海葵毒素和增加细胞外钾离子浓度。本研究旨在检测不同 Abeta 肽是否会特异性影响β样振荡模式。我们具体检测了新鲜溶解 Abeta(25-35)和寡聚 Abeta(1-42)的作用,发现两种 Abeta 都可浓度依赖性地影响海葵毒素诱导的振荡网络活动,且新鲜溶解 Abeta(25-35)(主要为单体)的影响更显著。相反,寡聚 Abeta(1-42)降低钾离子诱导的振荡活动,但单体 Abeta(25-35)对任何测试浓度的振荡活动均无影响。综上,我们的研究结果支持这样一种观点,即不同的淀粉样蛋白肽可能会改变与特定神经元网络活动产生相关的特定细胞机制,而非 Abeta 肽对神经元网络功能的普遍抑制作用。