Toll-like receptor 4-mediated signaling participates in apoptosis of hippocampal neurons

• Published in: Neural regeneration research 2013-10, Vol.8 (29), p.2744-2753
• Main Authors: He, Yue, Zhou, Ailing, Jiang, Wei
• Format: Article
• Language: English
• Subjects: Apoptosis; Caspase-3; Cellular signal transduction; Hippocampus (Brain); Physiological aspects; Technique and Method : Basic Research in Neural Regeneration; Toll-like receptors; Toll样受体4; 介导; 信号传导途径; 抗细胞凋亡; 海马神经元; 磷脂酰肌醇3激酶; 胱天蛋白酶-3
• ISSN: 1673-5374; 1876-7958
• DOI: 10.3969/j.issn.1673-5374.2013.29.006

The phosphatidylinositol 3 kinase （PI3K）/protein kinase B （AKT） signaling pathway is considered important for cell survival and has been shown to mediate various anti-apoptotic biological effects. This study explored the role of the Toll-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-3βSserg in hippocampal neurons stimulated by lipopolysaccharide 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, de-creased before intervention with lipopolysaccharide, but increased after treatment with the AKT in-hibitor, LY294002. These findings suggest that the TLR4-PI3K/AKT-GSKβ signaling pathway may be involved in lipopolysaccharide-induced apoptosis of hippocampal neurons.