Pterostilbene Improves Cognitive Performance in Aged Rats: An in Vivo Study

Cell Physiol Biochem. 2019;52(2):232-239. doi: 10.33594/000000017. Epub 2019 Feb 28.


Background/aims: Pterostilbene (Pt; trans-3,5-dimethoxy-4'-hydroxystilbene) is a natural phenol found in blueberries and grapevines. It shows remarkable biomedical activities similar to those of resveratrol. Its high bioavailability is a major advantage for possible biomedical applications. The goal of the study was to evaluate the effects of chronic pterostilbene administration on cognitive performance in aged rats with mild cognitive impairment.

Methods: 18-month-old animals were subjected to behavioral tests to establish the "baseline", then divided into treatment and control groups. The former were chronically fed Pt (22.5 mg/kg-day) for 20 consecutive days. At the end of this period all animals were tested again and sacrificed. The dentate gyrus, the hippocampus and the prefrontal and perirhinal cortices were then collected, and RT-qPCR and/or Western blot analyses were performed on a few transcripts/proteins involved in synaptic remodeling. Mitochondrial content was also assessed.

Results: Pt administration improved performance in behavioral tests and positively affected memory consolidation. We found increased levels of REST, PSD-95 and mitochondrial porin1 in the dentate gyrus and a positive correlation between T-maze test score and levels of cAMP responsive element binding protein (CREB) phosphorylation.

Conclusion: These results underscore the therapeutic potential of Pt supplementation for age-related cognitive decline.

Keywords: Aging; Cognitive decline; Object in context; Object recognition; Pterostilbene; Synaptic plasticity; T-maze.

MeSH terms

  • Aging / metabolism*
  • Animals
  • Behavior, Animal / drug effects*
  • CREB-Binding Protein / metabolism
  • Cognition / drug effects*
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / pathology
  • Dentate Gyrus / metabolism
  • Disks Large Homolog 4 Protein / biosynthesis
  • Maze Learning / drug effects*
  • Rats
  • Repressor Proteins / biosynthesis
  • Stilbenes / pharmacology*


  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • RE1-silencing transcription factor
  • Repressor Proteins
  • Stilbenes
  • pterostilbene
  • CREB-Binding Protein
  • Crebbp protein, rat