Xanthohumol improved cognitive flexibility in young mice

Behav Brain Res. 2014 Dec 15:275:1-10. doi: 10.1016/j.bbr.2014.08.045. Epub 2014 Sep 1.


The protein palmitoylation cycle has been shown to be important for protein signaling and synaptic plasticity. Data from our lab showed a change in the palmitoylation status of certain proteins with age. A greater percentage of the NMDA receptor subunits GluN2A and GluN2B, along with Fyn and PSD95 proteins, were palmitoylated in the old mice. The higher level of protein palmitoylation was also associated with poorer learning scores. Xanthohumol is a prenylated flavonoid that has been shown to increase beta-oxidation in the livers of rodents, decreasing circulating free fatty acids in the serum. What is not known is whether the application of xanthohumol could influence the palmitoylation status of proteins. In this study, young and old mice were fed a diet supplemented with xanthohumol for 8 weeks. Spatial memory was assessed with the Morris water maze and protein palmitoylation quantified. The young xanthohumol-treated mice showed a significant improvement in cognitive flexibility. However, this appeared to be associated with the young control mice, on a defined, phytoestrogen-deficient diet, performing as poorly as the old mice and xanthohumol reversing this effect. The old mice receiving xanthohumol did not significantly improve their learning scores. Xanthohumol treatment was unable to affect the palmitoylation of NMDA receptor subunits and associated proteins assessed in this study. This evidence suggests that xanthohumol may play a role in improving cognitive flexability in young animals, but it appears to be ineffective in adjusting the palmitoylation status of neuronal proteins in aged individuals.

Keywords: Aging; Memory; Palmitate; Palmitoylation; Reversal trials.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging
  • Analysis of Variance
  • Animals
  • Body Weight / drug effects
  • Cognition / drug effects*
  • Disks Large Homolog 4 Protein
  • Fatty Acids / metabolism
  • Flavonoids / metabolism
  • Flavonoids / pharmacology*
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism
  • Gene Expression Regulation / drug effects
  • Guanylate Kinases
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Maze Learning / drug effects
  • Membrane Proteins
  • Mice
  • Propiophenones / metabolism
  • Propiophenones / pharmacology*
  • Proto-Oncogene Proteins c-fyn
  • Receptors, N-Methyl-D-Aspartate
  • Tissue Distribution / drug effects


  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Fatty Acids
  • Flavonoids
  • Membrane Proteins
  • NR2B NMDA receptor
  • Propiophenones
  • Receptors, N-Methyl-D-Aspartate
  • Fyn protein, mouse
  • Proto-Oncogene Proteins c-fyn
  • Guanylate Kinases
  • xanthohumol
  • N-methyl D-aspartate receptor subtype 2A