Ciliary neurotrophic factor has neuroprotective effects mediated through signal transducer and Janus kinase（JAK） 2/activator of transcription 3（STAT3） and phosphatidylinositol 3-kinase（PI3 K）/Akt signaling pathw...Ciliary neurotrophic factor has neuroprotective effects mediated through signal transducer and Janus kinase（JAK） 2/activator of transcription 3（STAT3） and phosphatidylinositol 3-kinase（PI3 K）/Akt signaling pathways.Whether ciliary neurotrophic factor is neuroprotective for glutamate-induced excitotoxicity of dorsal root ganglion neurons is poorly understood.In the present study,the in vitro neuroprotective effects of ciliary neurotrophic factor against glutamate-induced excitotoxicity were determined in a primary culture of dorsal root ganglion neurons from Wistar rat embryos at embryonic day 15.Whether the JAK2/STAT3 and PI3 K/Akt signaling pathways were related to the protective effects of ciliary neurotrophic factor was also determined.Glutamate exposure inhibited neurite outgrowth,cell viability,and growth-associated protein 43 expression and promoted apoptotic neuronal cell death,all of which were reversed by the administration of exogenous ciliary neurotrophic factor.Additionally,preincubation with either JAK2 inhibitor AG490 or PI3 K inhibitor LY294002 blocked the neuroprotective effect of ciliary neurotrophic factor.These data indicate that the two pathways JAK2/STAT3 and PI3 K/Akt play major roles in mediating the in vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity.展开更多
基金supported by the Natural Science Foundation of Shandong Province of China,No.ZR2014HQ065a grant from the Medical Science and Technology Development Project of Shandong Province of China,No.2015WS0445
文摘Ciliary neurotrophic factor has neuroprotective effects mediated through signal transducer and Janus kinase（JAK） 2/activator of transcription 3（STAT3） and phosphatidylinositol 3-kinase（PI3 K）/Akt signaling pathways.Whether ciliary neurotrophic factor is neuroprotective for glutamate-induced excitotoxicity of dorsal root ganglion neurons is poorly understood.In the present study,the in vitro neuroprotective effects of ciliary neurotrophic factor against glutamate-induced excitotoxicity were determined in a primary culture of dorsal root ganglion neurons from Wistar rat embryos at embryonic day 15.Whether the JAK2/STAT3 and PI3 K/Akt signaling pathways were related to the protective effects of ciliary neurotrophic factor was also determined.Glutamate exposure inhibited neurite outgrowth,cell viability,and growth-associated protein 43 expression and promoted apoptotic neuronal cell death,all of which were reversed by the administration of exogenous ciliary neurotrophic factor.Additionally,preincubation with either JAK2 inhibitor AG490 or PI3 K inhibitor LY294002 blocked the neuroprotective effect of ciliary neurotrophic factor.These data indicate that the two pathways JAK2/STAT3 and PI3 K/Akt play major roles in mediating the in vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity.
