Low-dose Pterostilbene, but Not Resveratrol, Is a Potent Neuromodulator in Aging and Alzheimer's Disease

Neurobiol Aging. 2012 Sep;33(9):2062-71. doi: 10.1016/j.neurobiolaging.2011.08.015. Epub 2011 Oct 7.

Abstract

Recent studies have implicated resveratrol and pterostilbene, a resveratrol derivative, in the protection against age-related diseases including Alzheimer's disease (AD). However, the mechanism for the favorable effects of resveratrol in the brain remains unclear and information about direct cross-comparisons between these analogs is rare. As such, the purpose of this study was to compare the effectiveness of diet-achievable supplementation of resveratrol to that of pterostilbene at improving functional deficits and AD pathology in the SAMP8 mouse, a model of accelerated aging that is increasingly being validated as a model of sporadic and age-related AD. Furthermore we sought to determine the mechanism of action responsible for functional improvements observed by studying cellular stress, inflammation, and pathology markers known to be altered in AD. Two months of pterostilbene diet but not resveratrol significantly improved radial arm water maze function in SAMP8 compared with control-fed animals. Neither resveratrol nor pterostilbene increased sirtuin 1 (SIRT1) expression or downstream markers of sirtuin 1 activation. Importantly, markers of cellular stress, inflammation, and AD pathology were positively modulated by pterostilbene but not resveratrol and were associated with upregulation of peroxisome proliferator-activated receptor (PPAR) alpha expression. Taken together our findings indicate that at equivalent and diet-achievable doses pterostilbene is a more potent modulator of cognition and cellular stress than resveratrol, likely driven by increased peroxisome proliferator-activated receptor alpha expression and increased lipophilicity due to substitution of hydroxy with methoxy group in pterostilbene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / blood
  • Aging / drug effects*
  • Aging / genetics
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Analysis of Variance
  • Animals
  • Biological Availability
  • Brain / drug effects
  • Brain / metabolism
  • Dietary Supplements
  • Disease Models, Animal
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Gene Expression Regulation / drug effects
  • MAP Kinase Kinase 4 / metabolism
  • Male
  • Maze Learning / drug effects
  • Mice
  • Neurotransmitter Agents / administration & dosage*
  • Neurotransmitter Agents / blood
  • PPAR alpha / metabolism
  • Phosphorylation / drug effects
  • Protein-Serine-Threonine Kinases / metabolism
  • Resveratrol
  • Signal Transduction / drug effects
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Stilbenes / administration & dosage*
  • Stilbenes / blood
  • tau Proteins / metabolism

Substances

  • Neurotransmitter Agents
  • PPAR alpha
  • Stilbenes
  • tau Proteins
  • pterostilbene
  • Protein-Serine-Threonine Kinases
  • NF-kappa B kinase
  • MAP Kinase Kinase 4
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Resveratrol