PNS Prevents Lipopolysaccharide-induced Depression-like Behavior Through The Inhibition Of Hippocampal Microglia Activation In Mice

[Objective] Following a depression mice model induced by lipopolysaccharide(LPS),we investigated the effects of Panax Notoginseng Saponins(PNS)on depression-like behavior and its underlying mechanism.[Method](1)Animal grouping: 200 male Kunming mice(25-32g)were randomly assigned into five groups: Vehicle group,LPS group,LPS+different dose of PNS pre-treatment group(50/100/200mg/kg PNS+LPS group),LPS+fluoxetine pretreatment group(FLX+LPS)and different dose of PNS group(50/100/200mg/kg PNS group);(2)Model building:The depression mice were established with intraperitoneal injection of LPS(0.5mg/kg);(3)Behavioral detecting:Sickness behavior were tested by the changes of body weight and feeding intake behavior,anhedonia behavior were judged by sucrose preference test and sucrose splash test,learned helplessness behavior were valuated by forced swimming test,Locomotivity were estimated by open field test;(4)Biochemical detecting:Immunohistochemistry was performed to investigate the expression of IBA-1(a microglia marker)and DCX(a marker of neuronal precursors)in hippocampus of each group mice,the expression of IBA-1,CD68,NF-κB,IKKβ,DCX and Nestin was measured by Western blotting,RT-PCR was used to detect the m RNA level of IL-1β and TNFα in hippocampus.[Results](1)Compared with the Vehicle group,LPS mice exhibited a significantly weight loss,food intake reduction,sucrose preference percentage declination,the shorter splash biting time and the longer immobility time in forced swimming test(P<0.05 in all);Versus the LPS group,mice in the PNS+LPS group,100mg/kg PNS was the best dose among those three different dose,showed that the lightened weight loss,the increased food intake,the raised sucrose preference percentage,the prolonged splash biting time and the shortened immobility time in forced swimming test(P<0.05 in all),FLX pretreatment had the similar effects as PNS,which reversed the behavior induced by LPS: the food intake reduction,the shorter splash biting time and the longer immobility time in forced swimming test(P<0.05 in all);Versus the Vehicle group,delivery of PNS at three doses(30,100,300 lg/kg)made no discernible effects on the locomotivity,the sucrose preference percentage,the immobility time(P>0.05 in all);(2)LPS mice exhibited significantly increased expression of IBA-1 and CD68 in hippocampus compared with the Vehicle group(P<0.05),prophylactic application of PNS remarkably inhibited the increase of IBA-1 and CD68(P<0.05);(3)Compared with the vehicle group,LPS mice showed a distinctly upregulation of NF-κB(P<0.05)and degradation of IKKβ in hippocampus,treatment with PNS reversed the expression of NF-κB and IKKβ in LPS-mice(P<0.05);(4)The m RNA expression levels of IL-1β and TNFα in the hippocampus of LPS mice were significantly higher than that of vehicle mice(P<0.05),PNS treatment strongly inhibited the changes in IL-1β and TNFα induced by LPS(P<0.05);(5)Compared with the vehicle group,mice in the LPS group exhibited both significantly down-regulation DCX and Nestin in hippocampus(P<0.05),application of PNS upregulated the LPS-induced the expression of DCX and Nestin(P<0.05).[Conclusion] PNS possesses the function of relieving depression-like behavior induced by LPS,which is correlated with its inhibition of microglia in hippocampus,reduction of the central inflammatory cytokines and protection of neurogenesis eventually.