Department of Drug Science and Technology, Turin University, Corso Raffaello 30, 10125, Torino, Italy; Akdeniz University Faculty of Medicine Department of Biophysics, Antalya, Turkey.
Akdeniz University Faculty of Medicine Department of Biophysics, Antalya, Turkey.
Adv Med Sci. 2022 Sep;67(2):328-337. doi: 10.1016/j.advms.2022.08.003. Epub 2022 Sep 1.
We aimed to determine the effects of different doses of amyloid-beta (Aβ) peptide on learning and memory, and whether the changes in brain oscillations induced by dose-dependent accumulation of Aβ could be used as biomarkers to detect early stages of Alzheimer's disease (AD).
Male albino Wistar rats aged 3 months were randomly divided into four groups (n = 12/group) obtained by i. h. Injection (to the dorsal hippocampus) of saline or different doses of 0.01 μg/μl, 0.1 μg/μl, and 1 μg/μl of Aβ. After two weeks of recovery period, open field and novel object recognition tests were performed and spontaneous EEG recordings were obtained. Later, hippocampus tissues were collected for Western blot and ELISA analysis.
A significant decrement in recognition memory was observed in 0.1 μg/μl, and 1 μg/μl injected groups. In addition, Aβ accumulation induced significant decrement of the expression of NeuN, SNAP-25, SYP, and PSD-95 proteins, and led to the increment of GFAP expression in hippocampus. Moreover, we detected remarkable alterations in spontaneous brain activity. The hippocampal Aβ levels were negatively correlated with hippocampal gamma power and positively correlated with hippocampal theta power. Also, we observed significant changes in coherence values, indicating the functional connectivity between different brain regions, after the accumulation of Aβ. Especially, there was a significant correlation between changes in frontohippocampal theta coherence and in frontotemporal theta coherence.
Our findings indicate that Aβ peptide induces AD-like molecular changes at certain doses, and these changes could be detected by evaluating brain oscillations.
本研究旨在探讨不同剂量的β淀粉样蛋白（Aβ）肽对学习和记忆的影响，以及 Aβ 剂量依赖性积累引起的脑振荡变化是否可作为检测阿尔茨海默病（AD）早期的生物标志物。
将 3 月龄雄性白化 Wistar 大鼠随机分为 4 组（n = 12/组），通过海马内注射（背部）生理盐水或 0.01μg/μl、0.1μg/μl 和 1μg/μl 的不同剂量 Aβ 进行分组。两周恢复期后，进行旷场和新物体识别测试，并进行自发脑电记录。随后收集海马组织进行 Western blot 和 ELISA 分析。
在 0.1μg/μl 和 1μg/μl 注射组观察到识别记忆显著下降。此外，Aβ 积累导致 NeuN、SNAP-25、SYP 和 PSD-95 蛋白表达显著下降，并导致海马 GFAP 表达增加。此外，我们检测到自发脑活动的显著改变。海马 Aβ 水平与海马γ功率呈负相关，与海马θ功率呈正相关。而且，我们观察到相干值发生显著变化，表明 Aβ 积累后不同脑区之间的功能连接发生改变。特别是，额-海马θ相干性和额-颞叶θ相干性的变化之间存在显著相关性。
我们的研究结果表明，Aβ 肽在一定剂量下诱导 AD 样分子变化，这些变化可以通过评估脑振荡来检测。
