Previous evidence has suggested that dietary supplementation with a bioactive dietary polyphenol preparation(BDPP)rescues impairment ofhippocampus-dependentmemory in amousemodelof sleepdeprivation (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 metabolismof dietary BDPP that are responsible for the attenuation of SD-mediated memory impairments. On the basis of high-throughput bioavailability studies of brain bioavailablemetabolites after dietaryBDPP treatment,we found that select polyphenol metabolites [e.g., cyanidin-39-O-glucoside and 3-(39-hydroxyphenyl) propionic acid] were able to rescuemTORand p70S6K phosphorylation in primary cortico-hippocampal neuronal cultures, aswell 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., ... Pasinetti, G. M. (2018). Dietary polyphenols promote resilience against sleep deprivation-induced cognitive impairment by activating protein translation. FASEB Journal, 32(10), 539-5404. https://doi.org/10.1096/fj.201800030R