Grape-derived polyphenols produce antidepressant effects via vgf-and bdnf-dependent mechanisms

Cheng Jiang, Emmy Sakakibara, Wei Jye Lin, Jun Wang, Giulio M. Pasinetti, Stephen R. Salton

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

8 Scopus citations


Recent studies suggest that bioactive dietary polyphenol preparation (BDPP) and individual polyphenolic compounds ameliorate stress-induced depression-like behaviors, but the underlying molecular mechanisms are incompletely understood. VGF (non-acronymic) in the dorsal hippocampus (dHc) has been shown to play a role in depression-like behaviors and antidepressant efficacy, and the VGF-derived peptide TLQP-62 (named by the N-terminal 4 amino acids and length) infused into dHc has been shown to have antidepressant efficacy that is BDNF– TrkB dependent. Here, we investigated whether BDPP influences VGF expression in the dHc, and whether dHc VGF is required for BDPP antidepressant efficacy. We found that BDPP produced antidepressant-like effects in naive mice and reversed the depression-like behaviors induced by chronic variable stress. In addition, we found that BDPP had no detectable antidepressant efficacy in floxed mice with prior knockdown in the dHc of either VGF or BDNF, achieved by adeno-associated virus-Cre infusion. Our data indicate that dHc VGF and BDNF expression are required for the antidepressant actions of BDPP, and therefore suggest that a VGF(TLQP-62)–BDNF–TrkB autoregulatory feedback loop could play a role in the regulation of BDPP antidepressant efficacy, much as it has been suggested to function in the antidepressant efficacies of ketamine and TLQP-62.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
PublisherBlackwell Publishing Inc.
Number of pages10
StatePublished - 2019

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • Antidepressant
  • Brain-derived neurotrophic factor (BDNF)
  • Chronic variable stress (CVS)
  • Grape seed polyphenolic extract (GSPE)
  • Major depressive disorder (MDD)
  • Polyphenol


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