TitleXanthohumol improved cognitive flexibility in young mice.
Publication TypeJournal Article
Year of Publication2014
AuthorsZamzow DR, Elias V, Legette LCL, Choi J, J Stevens F, Magnusson KR
JournalBehav Brain Res
Date Published2014 Dec 15
KeywordsAging, Analysis of Variance, Animals, Body Weight, Cognition, Disks Large Homolog 4 Protein, Fatty Acids, Flavonoids, Frontal Lobe, Gene Expression Regulation, Guanylate Kinases, Hippocampus, Male, Maze Learning, Membrane Proteins, Mice, Propiophenones, Proto-Oncogene Proteins c-fyn, Receptors, N-Methyl-D-Aspartate, Tissue Distribution

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.

Alternate JournalBehav. Brain Res.
PubMed ID25192637
PubMed Central IDPMC4281268
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
R01 AG016322 / AG / NIA NIH HHS / United States
AG16322 / AG / NIA NIH HHS / United States
P30ES000210 / ES / NIEHS NIH HHS / United States