In vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity

• Published in: Neural regeneration research Vol. 12; no. 10; pp. 1716 - 1723
• Main Authors: Wen, Shu-Yun, Li, Ai-Min, Mi, Kuan-Qing, Wang, Rui-Zheng, Li, Hao, Liu, Hua-Xiang, Xing, Yi
• Format: Journal Article
• Language: English
• Published: India Medknow Publications and Media Pvt. Ltd 01.10.2017; Medknow Publications & Media Pvt. Ltd; Department of Rheumatology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China%Department of Rheumatology, Qingdao Fifth People's Hospital, Qingdao, Shandong Province, China%Department of Neurosurgery, Jinan Fifth People's Hospital, Jinan, Shandong Province, China%Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, Shandong Province, China%Department of Rheumatology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China%Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China; Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Analysis; Cell culture; Ciliary neurotrophic factor; Dorsal root ganglia; Glutamate; Health aspects; Labeling; Laboratory animals; nerve regeneration; ciliary neurotrophic factor; JAK2/STAT3; PI3K/Akt; glutamate; neuron; excitotoxicity; neuroprotection; growth-associated protein 43; neurite outgrowth; dorsal root ganglion; neural regeneration; Neurons; Neurotoxic agents; Neurotoxicity; Proteins; Wistar大鼠; 兴奋性毒性; 睫状神经营养因子; 磷脂酰肌醇3-激酶; 神经保护作用; 背根神经节神经元; 诱导; 谷氨酸; United States > US; China; neural regeneration; neuroprotection; dorsal root ganglion; neuron; JAK2/STAT3; growth-associated protein 43; nerve regeneration; neurite outgrowth; excitotoxicity; ciliary neurotrophic factor; glutamate; PI3K/Akt
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.217352

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.