title: Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease.
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.
authors: Department of Neuroscience, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Jaewon
authors: J
authors: Chang
authors: Agnes
authors: A
authors: Rimando
authors: Merce
authors: M
authors: Pallas
authors: Antoni
authors: A
authors: Camins
authors: David
authors: D
authors: Porquet
authors: Jennifer
authors: J
authors: Reeves
authors: Barbara
authors: B
authors: Shukitt-Hale
authors: Mark A
authors: MA
authors: Smith
authors: James A
authors: JA
authors: Joseph
authors: Gemma
authors: G
authors: Casadesus
mesh_terms: D000375:Aging / Q000097:blood / Q000187:drug effects* / Q000235:genetics; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005786:Gene Expression Regulation / Q000187:drug effects; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018377:Neurotransmitter Agents / Q000008:administration & dosage* / Q000097:blood; D047493:PPAR alpha / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage* / Q000097:blood; D016875:tau Proteins / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D048670:MAP Kinase Kinase 4; D018377:Neurotransmitter Agents; D047493:PPAR alpha; D017346:Protein Serine-Threonine Kinases; D000077185:Resveratrol; D056564:Sirtuin 1; D013267:Stilbenes; D016875:tau Proteins; D000097782:NF-kappaB-Inducing Kinase; C107773:pterostilbene; C470545:Sirt1 protein, mouse