We recently identified, in preclinical studies, specific polyphenol-rich botanical dietary supplements [e.g., grape seed polyphenol extract (GSPE), Concord grape juice (CGJ), and resveratrol (RSV)] that are effective in promoting cognitive and psychological resilience under stress conditions. The overall goal of the proposed Botanical Dietary Supplement Research Center (BDSRC) is to identify the specific polyphenol components from these bioactive botanical supplements that underlie their bioactivities and to characterize specific cellular/molecular mechanisms contributing to the attenuation of physiological stress, such as that associated to stressful life events, that have detrimental impact on psychological health, cognitive functions, and ultimately wellbeing (Projects 1-2). In addition the proposed studies will, for the first time, clarify the role of the gastrointestinal (G) microbiome, particularly the human GI microbiome, in modulating the bioavailability of polyphenol components responsible for the cognitive and psychological health benefits of dietary polyphenol botanical supplements using humanized gnotobiotic mice (Project 3). Thus, the proposed studies, which (1) characterize botanicals, (2) assess, pre-clinically, their bioavailability and bioactivity in the periphery and in the brain, while defining molecular mechanisms of resilience, and (3) identify safety issues essential for future development into clinical application, are in full alignment with the goals of NCCAM and ODS, as indicated in the Research Objectives of the RFA. The proposed studies in this BDSRC will improve scientific knowledge and technical capabilities through the development of a rigorous scientific program, will provide training and career development opportunities, and, critically, will provide an intellectually rigorous examination of the role of dietary polyphenol botanical supplements in the maintenance and promotion of psychological and cognitive resilience.
Promoting psychological and cognitive resilience in response to external stressors is one of the most difficult challenges to brain wellness. The proposed research in this BDSRC will provide a unique and detailed dissection of the role of dietary polyphenolic botanical supplements in the maintenance and promotion of psychological and cognitive resilience in models of social defeat and sleep deprivation.
|Novotny, Janet A; Chen, Tzu-Ying; Terekhov, Anton I et al. (2017) The effect of obesity and repeated exposure on pharmacokinetic response to grape polyphenols in humans. Mol Nutr Food Res 61:|
|Flanigan, Meghan; Aleyasin, Hossein; Takahashi, Aki et al. (2017) An emerging role for the lateral habenula in aggressive behavior. Pharmacol Biochem Behav 162:79-86|
|Chen, Tzu-Ying; Ferruzzi, Mario G; Wu, Qing-Li et al. (2017) Influence of diabetes on plasma pharmacokinetics and brain bioavailability of grape polyphenols and their phase II metabolites in the Zucker diabetic fatty rat. Mol Nutr Food Res 61:|
|Ménard, Caroline; Pfau, Madeline L; Hodes, Georgia E et al. (2017) Immune and Neuroendocrine Mechanisms of Stress Vulnerability and Resilience. Neuropsychopharmacology 42:62-80|
|Takahashi, Aki; Chung, Jia-Ru; Zhang, Song et al. (2017) Establishment of a repeated social defeat stress model in female mice. Sci Rep 7:12838|
|Mosley, Grace E; Evashwick-Rogler, Thomas W; Lai, Alon et al. (2017) Looking beyond the intervertebral disc: the need for behavioral assays in models of discogenic pain. Ann N Y Acad Sci 1409:51-66|
|Menard, Caroline; Pfau, Madeline L; Hodes, Georgia E et al. (2017) Social stress induces neurovascular pathology promoting depression. Nat Neurosci 20:1752-1760|
|Hodes, Georgia E; Walker, Deena M; Labonté, Benoit et al. (2017) Understanding the epigenetic basis of sex differences in depression. J Neurosci Res 95:692-702|
|Pfau, Madeline L; Purushothaman, Immanuel; Feng, Jian et al. (2016) Integrative Analysis of Sex-Specific microRNA Networks Following Stress in Mouse Nucleus Accumbens. Front Mol Neurosci 9:144|
|Golden, Sam A; Heshmati, Mitra; Flanigan, Meghan et al. (2016) Basal forebrain projections to the lateral habenula modulate aggression reward. Nature 534:688-92|
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