Intracerebroventricular injection of resveratrol ameliorated Aβ-induced learning and cognitive decline in mice

Metab Brain Dis. 2019 Feb;34(1):257-266. doi: 10.1007/s11011-018-0348-6. Epub 2018 Nov 20.

Abstract

Resveratrol (RSV) is a natural plant polyphenol compound which consists in red grape skins and wine in general. Plenty of previous studies have shown that resveratrol has neuroprotective effects. The primary object of this research was to study the effects of RSV on improving the cognitive function and neurodegeneration in the mouse model of Alzheimer's disease induced by Aβ1-42, and the possible mechanism about targeting on Sirt1, which results in attenuating inflammatory response and mitochondrial dysfunction. We established the AD model of intracerebroventricular (i.c.v.) injection of Aβ1-42 and it was observed that the significant decrease in alternately of Y Maze and the quadrant dwell time percentage of Morris water maze test. Furthermore, there were significant upregulations of AMPK/ PGC-1α and downregulations of NF-κB/ IL-1β/ NLRP3 signaling pathways in the hippocampus and prefrontal cortex in AD mice. The treatments with RSV and Donepezil could significantly ameliorate all the behavioral and biochemical changes induced by Aβ1-42. It also noticeably improved the histopathological changes in the hippocampus and cortex. The results suggested that RSV might protect against cognitive deficits and neurodegeneration induced by Aβ1-42, and serve as a potential agent in treatment of AD.

Keywords: Alzheimer’s disease; Inflammation; Intracerebroventricular injection; Mitochondrial dysfunction; Resveratrol; Sirt1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Cognitive Dysfunction / drug therapy*
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Injections, Intraventricular
  • Learning / drug effects*
  • Male
  • Maze Learning / drug effects
  • Mice
  • NF-kappa B / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Resveratrol / administration & dosage*
  • Resveratrol / therapeutic use
  • Signal Transduction / drug effects
  • Sirtuin 1 / metabolism
  • Spatial Memory / drug effects
  • Up-Regulation / drug effects

Substances

  • Amyloid beta-Peptides
  • NF-kappa B
  • Neuroprotective Agents
  • Sirtuin 1
  • Resveratrol