Research Paper Volume 8, Issue 5 pp 899—916

Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high-fat/sucrose diet

Michel Bernier1, , Devin Wahl1, , Ahmed Ali1, , Joanne Allard1,2, , Shakeela Faulkner1, , Artur Wnorowski3,4, , Mitesh Sanghvi4, , Ruin Moaddel4, , Irene Alfaras1, , Julie A. Mattison1, , Stefano Tarantini5, , Zsuzsanna Tucsek5, , Zoltan Ungvari5, , Anna Csiszar5, , Kevin J. Pearson1,6, , Rafael de Cabo1, ,

  • 1 Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA
  • 2 Department of Physiology and Biophysics, Howard University, College of Medicine, Washington, DC 20059, USA
  • 3 Department of Biopharmacy, Medical University of Lublin, 20-093 Lublin, Poland
  • 4 Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD 21224, USA
  • 5 University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
  • 6 Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA

Received: February 3, 2016       Accepted: March 30, 2016       Published: April 9, 2016
How to Cite

Copyright: © 2016 Bernier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Previous studies have shown positive effects of long-term resveratrol (RSV) supplementation in preventing pancreatic beta cell dysfunction, arterial stiffening and metabolic decline induced by high-fat/high-sugar (HFS) diet in nonhuman primates. Here, the analysis was extended to examine whether RSV may reduce dietary stress toxicity in the cerebral cortex of the same cohort of treated animals. Middle-aged male rhesus monkeys were fed for 2 years with HFS alone or combined with RSV, after which whole-genome microarray analysis of cerebral cortex tissue was carried out along with ELISA, immunofluorescence, and biochemical analyses to examine markers of vascular health and inflammation in the cerebral cortices. A number of genes and pathways that were differentially modulated in these dietary interventions indicated an exacerbation of neuroinflammation (e.g., oxidative stress markers, apoptosis, NF-κB activation) in HFS-fed animals and protection by RSV treatment. The decreased expression of mitochondrial aldehyde dehydrogenase 2, dysregulation in endothelial nitric oxide synthase, and reduced capillary density induced by HFS stress were rescued by RSV supplementation. Our results suggest that long-term RSV treatment confers neuroprotection against cerebral vascular dysfunction during nutrient stress.


RSV: resveratrol; 4-HNE: 4-hydroxynonenal; SD: standard diet; HFS: high-fat/high-sugar diet; HFS+R: HFS supplemented with resveratrol; eNOS: endothelial nitric oxide synthase; CSF: cerebral spinal fluid; VEGF: vascular endothelial growth factor; PCA: principal component analysis; PAGE: parametric analysis of gene-set enrichment; ROS: reactive oxygen species; GO terms: gene ontology terms; CNS: central nervous system; RT-PCR: real-time polymerase chain reaction; pVHL: von Hippel-Lindau protein; H2S: hydrogen sulfide; IL-6: interleukin 6; NF-κB: nuclear factor kappaB; COMMD: copper metabolism mURR1 domain containing; SIRT2: NAD+-dependent deacetylase 2; ALDH2: aldehyde dehydrogenase 2; TBI: trauma brain injury.