Some subtypes of endocannabinoid/endovanilloid receptors mediate docosahexaenoic acid-induced enhanced spatial memory in rats.

ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) enhances cognitive functions; however, the underlying molecular mechanism remains unclear. Compelling evidence suggests that the endocannabinoid/endovanilloid systems play a pivotal role in regulating cognitive function. Thus, to correlate the effect of DHA on cognitive performance with the expression of endocannabinoid and endovanilloid receptors, we supplemented the diet of rats with DHA and performed in vitro experiments that focused on the endocannabinoid/endovanilloid receptors. We found that in vivo supplementation with an appropriate dose of DHA (150 or 300mg/kg/d) significantly improved learning and memory but that a higher intake (600mg/kg/d) increased the risk of memory impairment. In addition, we found that some subtypes of endocannabinoid/endovanilloid receptors (cannabinoid [CB] and transient receptor potential vanilloid [TRPV] receptors) were regulated in vitro by different concentrations of DHA in primary hippocampal neuron culture medium. Real-time polymerase chain reaction and western blot analysis showed that expression of both CB1 and TRPV1 was upregulated in a dose-dependent manner and reached a maximum level at 30μmol/L (CB1) and 60μmol/L (TRPV1) DHA. However, TRPV2 expression was downregulated in a dose-dependent fashion, and the peak of TRPV2 suppression was observed at 60μmol/L. The dose-dependent effects of DHA on the expression of these receptors were well correlated with DHA's effect on spatial memory. Meanwhile, CB2, TRPV3, and TRPV4 expressions were not altered at diverse concentrations of DHA. We concluded that some subtypes of endocannabinoid/endovanilloid receptors might be involved in enhanced spatial memory induced by DHA supplementation.