EPA is More Effective than DHA to Improve Depression-Like Behavior, Glia Cell Dysfunction and Hippcampal Apoptosis Signaling in a Chronic Stress-Induced Rat Model of Depression

Abstract

Clinical evidence indicated that eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) in depression treatment. However, possible mechanisms remain unclear. Here, a chronic unpredictable mild stress (CUMS)-induced model of depression was used to compare EPA and DHA anti-depressant effects. After EPA or DHA feeding, depression-like behavior, brain n-3/n-6 PUFAs profile, serum corticosterone and cholesterol concentration, hippocampal neurotransmitters, microglial and astrocyte related function, as well as neuronal apoptosis and survival signaling pathways were studied. EPA was more effective than DHA to ameliorate CUMS-induced body weight loss, and depression-like behaviors, such as increasing sucrose preference, shortening immobility time and increasing locomotor activity. CUMS-induced corticosterone elevation was reversed by bother fatty acids, while increased cholesterol was only reduced by EPA supplement. Lower hippocampal noradrenaline and 5-hydroxytryptamine concentrations in CUMS rats were also reversed by both EPA and DHA supplement. However, even though CUMS-induced microglial activation and associated increased IL-1β were inhibited by both EPA and DHA supplement, increased IL-6 and TNF-α levels were only reduced by EPA. Compared to DHA, EPA could improve CUMS-induced suppressive astrocyte biomarkers and associated BDNF-TrkB signaling. Moreover, EPA was more effective than DHA to attenuate CUMS-induced higher hippocampal NGF, GDNF, NF-κB, p38, p75, and bax expressions, but reversed bcl-2 reduction. This study for the first time revealed the mechanisms by which EPA was more powerful than DHA in anti-inflammation, normalizing astrocyte and neurotrophin function and regulating NF-κB, p38 and apoptosis signaling. These findings reveal the different mechanisms of EPA and DHA in clinical depression treatment.

Dietary Eicosapentaenoic Acid and Docosahexaenoic Acid Ethyl Esters Influence the Gut Microbiota and Bacterial Metabolites in Rats

“…tended to have lower serum total cholesterol content p 0.09 than the DHA group. These findings were supported by a previous study where the EPA diet was found to be more effective at lowering serum total cholesterol content than the DHA diet 29 . In a human study, the increased HDLcholesterol level caused by DHA intake compared to EPA intake has been suggested to involve the inhibition of cholesteryl ester transfer protein CETP activity by DHA 30 .…”

A Reliable High-Throughput Screening Model for Antidepressant

“…The CUMS paradigm on mice was adapted from past research. In total, 11 different stressors were presented randomly twice a day for a total of 49 consecutive days [35][36][37].…”

New Insights into Depressive Disorder with Respect to Low-Grade Inflammation and Fish Oil Intake

“…A CMS study demonstrated that EPA and DHA can improve aberrant corticos-terone and IL-1β levels as well as hippocampal noradrenaline and 5-hydroxytryptamine concentrations. The researchers also reported that n-3 PUFAs can ameliorate microglial and astrocyte functions suppressed by CMS stimuli and improve depressive symptoms of rodent animals 88) . Notably, studies on models of brain development have indicated that n-3 PUFA supplementation reduces microglial activation or cause phenotype alteration.…”