【摘 要】
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Major depressive disorder is a neuropsychiatric disorder with few approaches.The application of nontargeted antidepressants induced many adverse effects including sexual dysfunction,cardiotoxicity and
【机 构】
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School of Life Science and Technology,Tongji University,1239 Siping Road,Shanghai
【出 处】
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中国生物化学与分子生物学会2016年全国学术会议
论文部分内容阅读
Major depressive disorder is a neuropsychiatric disorder with few approaches.The application of nontargeted antidepressants induced many adverse effects including sexual dysfunction,cardiotoxicity and sleeping trouble.Therefore,new approaches for major depression treatment are desirable.A more precise targeting strategy is to develop nanotechnology-based drug delivery systems,hence we employed solid lipid nanoparticles(SLNs)to encapsulate HU-211 and curcumin(Cur),the antidepressant effects of the dual-drug nanoparticles(Cur/SLNs-HU-211)for major depression treatment were investigated in corticosterone-induced cellular and animal models of major depressive disorder.Cur/SLNs-HU-211 can effectively protect PC12 cells from corticosterone-induced apoptosis and release more dopamine,which may associated with the higher uptake of Cur/SLNs-HU-211 showed by cellular uptake behaviour analysis.Additionally,Cur/SLNs-HU-211 significantly reduced the immobility time in forced swim test,enhanced fall latency in rotarod test,and improved the level of dopamine in mice blood.Cur/SLNs-HU-211 can deliver more curcumin to the brain and thus produce a significantly increase of neurotransmitters level in hippocampus and striatum.The results of western blot and immunofluorsecence all reveled that Cur/SLNs-HU-211 can significantly enhance the expressions of CB1,p-MEK1 and p-ERK1/2.Furthermore,we applied the CB1 receptor inhibitor Rimonabant in cellular and animal models of major depressive disorder,and we found that after treated with Cur/SLNs-HU-211 and Rimonabant,the protective effect of nanoparticles was weakened compared with no Rimonabant treated group.Our study suggested that Cur/SLNs-HU-211 may had great potential for major depression treatment.
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