The Molecular Mechanism Of Antarctic Krill Oil Treatment Ameliorating Chronic Unpredicted Mild Stress-induced Depressive-like Behaviors In Mice

Objective: Depression is one of the most common mental illnesses,which characterized as low mood,lack of pleasure,unwillingness to socialize and suicide thoughts in severe cases.The number of patients with depression continues to increase,but its pathogenesis is still unclear,which requires further research to reveal.More and more evidences show that the lack of n-3 polyunsaturated fatty acids(n-3 PUFAs)is related to the onset of depression,and n-3 PUFAs may be one of the potential treatments for depression.The unsaturated fatty acids in Antarctic krill oil is the only natural phospholipid type unsaturated fatty acids,which are easily absorbed by the body and enter the blood-brain barrier.In this study,to investigate the effects of Antarctic krill oil on CUMS-induced depressive-like behavior,the chronic unpredictable mild stress(CUMS)was used to produce depression-like behavior mice,and the lipid metabolomics and m RNA profiles in the whole brain were detected,which provided a new idea for the prevention and treatment of depression.Methods: Eight-week-old C57BL/6J mice were selected and randomly divided into four groups: Control+Water,Control+Oil,CUMS+Water and CUMS+Oil.CUMS+Water and CUMS+Oil groups treated with CUMS for four weeks.Sucrose preference test(SPT),forced swimming test(FST)and Y-maze test(YMT)were measured to evaluate the depression-like behavior of mice.The whole brain tissues from Control+Water,Control+Oil,CUMS+Water and CUMS+Oil group were obtained for transcriptional sequencing and lipid metabonomics,to evaluate the effect of Antarctic krill oil on the lipid homeostasis of brain tissue under CUMS treatment,and bioinformatics analysis methods and techniques were used to reveal the molecular mechanism of Antarctic krill oil on the occurrence of depression-like behaviors.Results: SPT,YMT and FST behavioral test results showed that CUMS-induced depression-like behaviors were ameliorated by Antarctic krill oil supplementary.The lipid metabonomics data showed that CUMS can induce significant differences in the levels of33 metabolites in the brain of mice.In addition,Antarctic krill oil significantly repaired the damage of the plasma membrane induced by CUMS in the brain,thereby ameliorated the homeostasis of lipids in the brain.Transcriptomics analysis results showed that CUMS induced significant changes in gene expression in the whole brain,and the differentially expressed genes were mainly enriched in the cholinergic metabolism,synaptic vesicle circulation,glutamatergic synapse,cholinergic synapse and metabolic pathways,which has been significantly ameliorated in the presence of Antarctic krill oil.Furthermore,115 differentially expressed genes(DEGs)related to CUMS treatment and155 DEGs related to Antarctic krill oil supplementary were identified.Conclusion: Depression-like behavior can be induced by CUMS treatments in mice,which can be ameliorated by Antarctic krill oil supplementary.Antarctic krill oil may repair the damage of CUMS to the plasma membrane and maintain the integrity of the plasma membrane to affect the neuroactive ligand-receptor interaction,thereby ameliorating the depression-like behavior induced by CUMS.This study revealed the effects of CUMS on lipid homeostasis and molecules in the brain of mice,and preliminarily investigated the molecular basis of Antarctic krill oil’s antidepressant,providing a new strategy for the prevention and treatment of depression.