Dietary EPA-Enriched Phospholipids Alleviate Chronic Stress and LPS-Induced Depression- and Anxiety-Like Behavior by Regulating Immunity and Neuroinflammation

Scope A growing number of studies have reported the effects of eicosapentaenoic acid (EPA) and terrestrial phospholipids on ameliorating mood disorders. Marine-derived EPA-enriched phospholipids (EPA-PL) exhibit the structural characteristics of EPA and phospholipids. However, the effect of dietary EPA-PL, and the differences between amphiphilic EPA-PL and lyophobic EPA on mood disorders had not been studied. Methods and Results A comparative investigation to determine the effects of dietary EPA-enriched ethyl ester (EPA-EE) and EPA-PL on improving depression- and anxiety-like behavior in a mouse model is performed, induced by 4 week chronic unpredictable mild stress (CUMS) coupled with lipopolysaccharide (LPS) challenge. It is found that dietary 4 week 0.6% (w/w) EPA-PL rescued depression- and anxiety-like behavior to a greater extent than did EPA-EE. Moreover, dietary EPA-PL significantly reduced the immobility time by 56.6%, close to the normal level, in forced swimming test, which revealed a reversal of depression-like behavior. Further studies revealed that dietary EPA-PL regulated immunity, monoamine systems, and the hypothalamic-pituitary-adrenal (HPA) axis by multi-target interactions, including inhibition of neuroinflammation and apoptosis. Conclusion EPA-PL exerted superior effects to EPA-EE in alleviating depression- and anxiety-like behavior. The data suggest potential novel candidate or targeted dietary patterns to prevent and treat mood disorder.

Automated summary

Comparative investigation showed that dietary EPA-PL had superior effects in alleviating depression- and anxiety-like behavior compared to EPA-EE. Further studies revealed that EPA-PL regulated immunity, monoamine systems, and the HPA axis through multi-target interactions, including inhibition of neuroinflammation and apoptosis.