Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease

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• 作者：Jaewon Chang ; Agnes Rim ; o ; Merce Pallas ; Antoni Camins ; David Porquet ; Jennifer Reeves ; Barbara Shukitt-Hale ; Mark A. Smith ; James A. Joseph ; Gemma Casadesus
• 关键词：Pterostilbene ; Resveratrol ; SAMP8 ; Alzheimer's disease ; Cognition ; Aging ; Cell signaling ; mnSOD ; NKF beta ; Tau ; PPAR alpha
• 刊名：Neurobiology of Aging
• 出版年：2012
• 出版时间：September, 2012
• 年：2012
• 卷：33
• 期：9
• 页码：2062-2071
• 全文大小：783 K

文摘

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.