Xanthohumol improved cognitive flexibility in young mice

Abstract

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.

Xanthohumol improves dysfunctional glucose and lipid metabolism in diet-induced obese C57BL/6J mice

“…Based on a previous study [27], we used a food intake of 2.7 g for a 30-g mouse to select the amounts of XN as 0.033% and 0.066% for the low XN and high XN diets, respectively. At 0.033% and 0.066% in the diet, the dose of XN was estimated to be 30 mg/kg body weight/day and 60 mg/kg body weight/day, respectively.…”

Inhibition of inflammation by astaxanthin alleviates cognition deficits in diabetic mice

“…In the eleventh week, mice in all groups were tested for learning and memory ability using the Morris water maze test [29,30]. The Morris water maze was composed of a large circular black pool (diameter: 120 cm; height: 50 cm, filled to a depth of 30 cm with water at 22 ± 2 C).…”

N-3 PUFAs and neuroinflammatory processes in cognitive disorders

“…As most receptors are embedded, damage to the membrane would disrupt all forms of neuronal communication (GomezPinilla et al, 2008). With ageing, lipid composition and fat deposition distribution are disturbed in the brain, most likely due to decreased liver peroxisomal β-oxidation (Yang et al, 2014;Zamzow et al, 2014), which is responsible for specific fatty acids synthesis such as DHA (Ferdinandusse et al, 2001). In addition, along with the decreased level and activity of the enzyme delta 6-desaturase (Yehuda et al, 2005), the higher cholesterol content in the ageing neuronal membrane decreases membrane fluidity of the BBB (Yehuda et al, 2002).…”