Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
The First Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Mol Med Rep. 2019 May;19(5):3783-3790. doi: 10.3892/mmr.2019.10010. Epub 2019 Mar 6.
Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder of the central nervous system that causes severe cognitive impairment. One of the most significant pathological features of AD is the accumulation of β‑amyloid (Aβ) peptide in the brain. Resveratrol (Res) is a polyphenol derived from peanuts, red grapes and other plants, which has received increasing attention due to its neuroprotective features. Tg6799 mice are transgenic mice with five familial AD (FAD) mutations that are also known as 5XFAD mice. The present study aimed to investigate the effects of Res on Tg6799 mice. The transgenic mice were randomly divided into the Res treatment group and the vehicle control group, and were treated with 0.5% Res solution (60 mg/kg) or volume‑matched normal saline, respectively. Treatment was administered by oral gavage daily for 60 consecutive days. Res reduced amyloid plaque formation and the levels of Aβ42, and β‑secretase 1 levels were also significantly decreased. Furthermore, Res was able to reduce the expression of amyloid precursor protein and its cleavage products. The administration of Res to Tg6799 mice also improved their spatial working memory, as measured by the Y‑maze test, and rescued spatial memory deficits, as measured using the Morris water maze test; however, Res did not affect their motor function. In conclusion, this study suggested that Res may reduce Aβ‑induced neuronal damage, thus preventing memory loss.
阿尔茨海默病（AD）是一种不可逆转的、进行性的中枢神经系统神经退行性疾病，可导致严重的认知障碍。AD 的最显著病理特征之一是大脑中β-淀粉样蛋白（Aβ）肽的积累。白藜芦醇（Res）是一种源自花生、红葡萄和其他植物的多酚，由于其神经保护特性而受到越来越多的关注。Tg6799 小鼠是具有五个家族性 AD（FAD）突变的转基因小鼠，也称为 5XFAD 小鼠。本研究旨在探讨 Res 对 Tg6799 小鼠的影响。将转基因小鼠随机分为 Res 治疗组和载体对照组，分别给予 0.5% Res 溶液（60mg/kg）或等体积的生理盐水，每日通过口服灌胃给药，连续 60 天。Res 减少了淀粉样斑块的形成和 Aβ42 水平，β-分泌酶 1 水平也显著降低。此外，Res 能够降低淀粉样前体蛋白及其裂解产物的表达。给予 Res 还改善了 Tg6799 小鼠的空间工作记忆，通过 Y 迷宫测试测量，挽救了空间记忆缺陷，通过 Morris 水迷宫测试测量；然而，Res 并未影响其运动功能。总之，本研究表明 Res 可能减少 Aβ 诱导的神经元损伤，从而预防记忆丧失。
