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Amyloid Beta Peptides Differentially Affect Hippocampal Theta Rhythms In Vitro

机译:淀粉样β肽体外差异影响海马θ节律。

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摘要

Soluble amyloid beta peptide (Aβ) is responsible for the early cognitive dysfunction observed in Alzheimer's disease. Both cholinergically and glutamatergically induced hippocampal theta rhythms are related to learning and memory, spatial navigation, and spatial memory. However, these two types of theta rhythms are not identical; they are associated with different behaviors and can be differentially modulated by diverse experimental conditions. Therefore, in this study, we aimed to investigate whether or not application of soluble Aβ alters the two types of theta frequency oscillatory network activity generated in rat hippocampal slices by application of the cholinergic and glutamatergic agonists carbachol or DHPG, respectively. Due to previous evidence that oscillatory activity can be differentially affected by different Aβ peptides, we also compared Aβ 25−35 and Aβ 1−42 for their effects on theta rhythms in vitro at similar concentrations (0.5 to 1.0 μM). We found that Aβ 25−35 reduces, with less potency than Aβ 1−42, carbachol-induced population theta oscillatory activity. In contrast, DHPG-induced oscillatory activity was not affected by a high concentration of Aβ 25−35 but was reduced by Aβ 1−42. 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 exerting a generalized inhibitory effect on neuronal network function.
机译:可溶性淀粉样蛋白β肽(Aβ)引起了在阿尔茨海默氏病中观察到的早期认知功能障碍。胆碱和谷氨酸引起的海马θ节律均与学习和记忆,空间导航和空间记忆有关。但是,这两种类型的theta节奏并不相同。它们具有不同的行为,并且可以通过各种实验条件进行差异调节。因此,在这项研究中,我们旨在研究可溶性Aβ的应用是否会分别通过胆碱能和谷氨酸能激动剂卡巴胆碱或DHPG的使用来改变大鼠海马切片中产生的两种θ频率振荡网络活动。由于先前的证据表明,不同的Aβ肽可以不同地影响振荡活动,因此我们还比较了Aβ25-35和Aβ1-42在相似浓度(0.5至1.0μM)下对体外theta节律的影响。我们发现,Aβ25-35降低了卡巴胆碱诱导的群体theta振荡活性,而其效力低于Aβ1-42。相反,DHPG诱导的振荡活性不受高浓度Aβ25-35的影响,但受Aβ1-42的影响而降低。我们的结果支持这样的想法,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的产生相关的特定细胞机制,而不是对神经元网络功能产生普遍的抑制作用。

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