Some Subtypes Of Endocannabinoid/endovanilloid Receptors Mediate Enhanced Spatial Memory Induced By Docosahexaenoic Acid Supplementation In Rats

Docosahexaenoic acid (DHA,22:6n-3) which exists in the phospholipid structure of cellular membrane of the brain and the major polyunsaturated fatty acid is essential for membrane continuity of normal neuronal function and it has gained more and more attention in cognition functions. During agingand in neurodegenerative disease such as Alzheimer's disease, the content of DHA in the brain declines. Chronic administration of DHA in a model of AD prevents?-amyloid deposition and impairment of memory ability function. In the study, we investigate whether DHA supplementation improves the spatial learning and memory ability of Sprague-Dawley (SD) male rats (2 months age) or not. In vivo, we found that DHA supplementations (at doses of 150 and 300 mg/kg/day) significantly improved learning and memory ability, but higher intake (600 mg/kg/day) increased the risk of memory impairment in rats. We concluded that DHA exerts bidirectional actions on cognition in vivo, namely, appropriate concentration of DHA improves cognition, but too high concentration might be harmful to the brain. Recently compelling evidences show that endocannabinoid/endovanilloid system appears to play a pivotal role in the regulation of cognition. We investigated the mechanism of DHA on learning and memory performance by exploiting whether endocannabinoid/endovanilloid receptors expressions in hippocampal neurons were regulated by DHA supplementation or not. In vitro, our most important finding was that some subtypes of endocannabinoid/endovanilloid receptors were regulated by DHA at different concentrations in primary hippocampal neuron culture medium. The results of Real-time PCR and Western blot showed that the expressions of CB1 and TRPV1 were both up-regulated in a dose-dependent manner and reached the maximum effect at 30?mol/L for CB1 and 60?mol/L for TRPV1 respectively. On the contrary, TRPV2 expression was down-regulated in a dose-dependent fashion and peak suppression was observed at 60?mol/L. The dose-dependent effects of DHA on the expression of these receptors were well in accordance with their effects on spatial memory. Meanwhile, CB2, TRPV3 and TRPV4 expressions were not altered by diverse concentrations of DHA. We concluded that some subtypes of endocannabinoid/endovanilloid receptors might be involved in enhanced spatial memory of DHA supplementation in rats. Some subtypes of endocannabinoid/endovanilloid receptors are involved in enhanced spatial memory of DHA supplementation in rats. To investigate whether the regulation on endocannabinoid/endovanilloid receptors expressions is exerted not only by DHA but also by other?-3 polyunsaturated fatty acid such as eicosapentaenoic acid (EPA), we evaluated the effect of EPA on them using the same methods. The results of Real-time PCR and Western blot showed that the expressions of CB1 was down-regulated in a dose-dependent manner and reached the maximum suppression at 100?mol/L. On the contrary, TRPV2 expression was up-regulated in a dose-dependent fashion and peak suppression was observed at 60?mol/L. Meanwhile, CB2, TRPV1, TRPV3 and TRPV4 expressions were not altered by diverse concentrations of EPA. We concluded that the complex gene regulations of EPA on endocannabinoid/endovanilloid receptors might be independent of the common property of?-3 polyunsaturated fatty acid.