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FASEB J. 2018 Oct;32(10):5390-5404. doi: 10.1096/fj.201800030R. Epub 2018 Apr 27.

Dietary polyphenols promote resilience against sleep deprivation-induced cognitive impairment by activating protein translation.

Author information

1
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
2
VUMC School of Medical Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
3
State University of New York at Stony Brook, Stony Brook, New York, USA.
4
Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA.

Abstract

Previous evidence has suggested that dietary supplementation with a bioactive dietary polyphenol preparation (BDPP) rescues impairment of hippocampus-dependent memory in a mouse model of sleep deprivation (SD). In the current study, we extend our previous evidence and demonstrate that a mechanism by which dietary BDPP protects against SD-mediated cognitive impairment is via mechanisms that involve phosphorylation of the mammalian target of rapamycin complex 1 and its direct downstream targets, including the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) and the ribosomal protein S6 kinase β-1 (p70S6K). In additional mechanistic studies in vitro, we identified the brain bioavailable phenolic metabolites derived from the metabolism of dietary BDPP that are responsible for the attenuation of SD-mediated memory impairments. On the basis of high-throughput bioavailability studies of brain bioavailable metabolites after dietary BDPP treatment, we found that select polyphenol metabolites [ e.g., cyanidin-3'- O-glucoside and 3-(3'-hydroxyphenyl) propionic acid] were able to rescue mTOR and p70S6K phosphorylation in primary cortico-hippocampal neuronal cultures, as well as rescue 4E-BP1 phosphorylation in response to treatment with 4EGI-1, a specific inhibitor of eIF4E-eIF4G interaction. Our findings reveal a previously unknown role for dietary polyphenols in the rescue of SD-mediated memory impairments via mechanisms involving the promotion of protein translation.-Frolinger, T., Smith, C., Cobo, C. F., Sims, S., Brathwaite, J., de Boer, S., Huang, J., Pasinetti, G. M. Dietary polyphenols promote resilience against sleep deprivation-induced cognitive impairment by activating protein translation.

KEYWORDS:

BDPP; mTORC1; memory consolidation

PMID:
29702026
PMCID:
PMC6133707
DOI:
10.1096/fj.201800030R
[Indexed for MEDLINE]
Free PMC Article

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