title: Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high-fat/sucrose diet.
abstract: 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.
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Bernier
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Wahl
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ali
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.|Department of Physiology and Biophysics, Howard University, College of Medicine, Washington, DC 20059, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Allard
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Shakeela
authors.initials: S
authors.lastname: Faulkner
authors.affiliation: Department of Biopharmacy, Medical University of Lublin, 20-093 Lublin, Poland.|Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Artur
authors.initials: A
authors.lastname: Wnorowski
authors.affiliation: Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Mitesh
authors.initials: M
authors.lastname: Sanghvi
authors.affiliation: Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Ruin
authors.initials: R
authors.lastname: Moaddel
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Alfaras
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Mattison
authors.affiliation: University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tarantini
authors.affiliation: University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Tucsek
authors.affiliation: University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
authors.affiliation: University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.|Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Pearson
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D059305:Diet, High-Fat; D019422:Dietary Sucrose; D020869:Gene Expression Profiling; D007249:Inflammation / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D019422:Dietary Sucrose; D016328:NF-kappa B; D018696:Neuroprotective Agents; D013267:Stilbenes; D052250:Nitric Oxide Synthase Type III; D000077185:Resveratrol
keywords: Rhesus monkeys; brain vasculature; cDNA microarray; endothelial nitric oxide synthase; inflammation