title: Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction.
abstract: Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction.
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Geriatric Research Education Clinical Center at James J. Peter VA Medical Center, Bronx, NY, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Geriatric Research Education Clinical Center at James J. Peter VA Medical Center, Bronx, NY, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Geriatric Research Education Clinical Center at James J. Peter VA Medical Center, Bronx, NY, USA.
authors.forename: Weina
authors.initials: W
authors.lastname: Bi
authors.affiliation: Department of Food Sciences, Purdue University, West Lafayette, IN, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Ferruzzi
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Shrishailam
authors.initials: S
authors.lastname: Yemul
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Freire
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Mazzola
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Geriatric Research Education Clinical Center at James J. Peter VA Medical Center, Bronx, NY, USA.
authors.forename: Lap
authors.initials: L
authors.lastname: Ho
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Dubner
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Geriatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Geriatric Research Education Clinical Center at James J. Peter VA Medical Center, Bronx, NY, USA. Electronic address: giulio.pasinetti@mssm.edu.
authors.forename: Giulio Maria
authors.initials: GM
authors.lastname: Pasinetti
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D056604:Grape Seed Extract / Q000008:administration & dosage* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D059808:Polyphenols / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012892:Sleep Deprivation / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D056604:Grape Seed Extract; D059808:Polyphenols; D013267:Stilbenes; D000077185:Resveratrol
keywords: Cognitive dysfunction; Memory consolidation; Polyphenols; Resilience; Sleep deprivation