Curcumin Mediates Antidepression-like Effect Via Regulation Of MTOR Signaling Pathway

Objective:To observe the effects of curcumin on the protection of SH-SY5Y cells from CORT-induced injury in mice with acute depression and mice with chronic stress depression,and to explore the molecular mechanism of mTOR in depression,and TREK-1-BDNF-mTOR signaling pathways in the antidepressant effect of curcumin,clear mTOR involved in the molecular mechanisms of depression and antidepressant effect and molecular mechanism of curcumin,as the development and application of antidepressants provide a new train of thought.Methods:The model of SH-SY5Y cells damaged by corticosterone was established.The cck-8 method was used to detect the protective effect of curcumin on corticosterone-induced SH-SY5Y cells and the CORT-induced SH-SY5Y cells pretreated with rapamycin.The morphology of cell synapses was observed under a microscope.The effects of curcumin on TREK-1,BDNF,p-p70s6k,p-ERK,p-mTOR and synapsin expression in SH-SY5Y cells were detected by western blot.Then,the mice forced swimming test?FST?,tail suspension test?TST?model of depression were established,and the mice were treated with rapamycin?ICV?which is mTOR specific inhibitor for 30min.The antidepressant effect of curcumin and the effect of mTOR signaling pathway on the behavior of mice were observed by gavage of curcumin 30min before the experiment.Results:In cell experiments,300?M of CORT significantly reduced cell survival.Co-culture with curcumin for 24h significantly increased the survival rate of CORT-induced SH-SY5Y cells(1?mol·L^-1,P<0.01;0.5?mol·L^-1,P<0.01;0.25?mol·L^-1,P<0.05);While rapamycin blocked the protective effect of curcumin?P<0.05?.By observing the morphological structure of synapses,axonal length was significantly reduced in the CORT group compared with the control group?P<0.001?.Compared with the CORT group,curcumin administration significantly increased axon length?P<0.05?.Co-culture with rapamycin reversed this effect?P<0.05?.Western blot results showed that the expressions of p-ERK,p-mTOR,p-p70s6k,and synapsin in SH-SY5Y cells damaged by CORT decreased significantly,and the expression level of TREK-1 increased.However,after treatment with curcumin,the expression levels of p-p70s6k in cells increased?P<0.05?,and the expression levels of TREK-1 decreased significantly?P<0.01?.The mTOR specific inhibitor rapamycin can inhibit the damage of curcumin on SH-SY5Y cells induced by CORT.Increased expression p-mtor is inhibited,The increased expression of p-mTOR,p-ERK,p-p70s6k and synapsin tended to be inhibited.Behavioral experiments showed that curcumin?50mg·kg-1?significantly reduced the immobility of forced swimming in mice compared with the control group?P<0.001?,reduced the accumulated immobility time of tail suspension experiment?P<0.05?.The effect of curcumin group pretreated with rapamycin?150nM,ICV?on the reduction of forced swimming immobility in mice was reversed?P<0.001?,the accumulated time of immobility increased in the tail suspension test of mice?P<0.01?.Conclusion:mTOR is involved in the occurrence and development of depression,,curcumin has obvious antidepressant effects,and its antidepressant mechanism may be related to the activation of mTOR signaling pathway,the blocking of TREK-1,and the increase of synaptic plasticity.