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The phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is considered important for cellsurvival and has been shown to mediate various anti-apoptotic biological effects. This study explored the role of the Tol -like receptor 4 (TLR4)-mediated PI3K/AKT-glycogen syn-thase kinase 3β (GSK-3β) signaling pathways in lipopolysaccharide-induced apoptosis in a primary culture of hippocampal neurons. Results demonstrated that the apoptotic ratio of hippocampal neurons stimulated by lipopolysaccharide was significantly higher compared with the control group. Both the expression of P-AKTSer473 and P-GSK-3βSer9 in hippocampal neurons stimulated by lipopo-polysaccharide decreased compared with the control, while the level of active Caspase-3 and the ratio of Bax/Bcl-2 were significantly increased. The level of active Caspase-3 and the ratio of Bax/Bcl-2 in hippocampal neurons treated with TLR4 antibody or the GSK-3β inhibitor, LiCl, creased before intervention with lipopolysaccharide, but increased after treatment with the AKT hibitor, LY294002. These findings suggest that the TLR4-PI3K/AKT-GSK3β signaling pathway may be involved in lipopolysaccharide-induced apoptosis of hippocampal neurons.
