Resveratrol improves cognition and decreases amyloid plaque formation in Tg6799 mice

Mol Med Rep. 2019 May;19(5):3783-3790. doi: 10.3892/mmr.2019.10010. Epub 2019 Mar 6.

Abstract

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.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Protein Precursor / physiology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Behavior, Animal / drug effects
  • Cognition Disorders / metabolism
  • Cognition Disorders / pathology
  • Cognition Disorders / prevention & control*
  • Disease Models, Animal*
  • Male
  • Memory Disorders / metabolism
  • Memory Disorders / pathology
  • Memory Disorders / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Plaque, Amyloid / prevention & control*
  • Presenilin-1 / physiology*
  • Resveratrol / pharmacology*

Substances

  • APP protein, human
  • Amyloid beta-Protein Precursor
  • Anti-Inflammatory Agents, Non-Steroidal
  • Presenilin-1
  • Resveratrol