Neural Regeneration Research ›› 2017, Vol. 12 ›› Issue (10): 1716-1723.doi: 10.4103/1673-5374.217352

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

 Shu-yun Wen1, 2, Ai-min Li3, Kuan-qing Mi4, Rui-zheng Wang4, Hao Li5, Hua-xiang Liu2, Yi Xing1   

  1. 1 Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China
    2 Department of Rheumatology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
    3 Department of Rheumatology, Qingdao Fifth People’s Hospital, Qingdao, Shandong Province, China
    4 Department of Neurosurgery, Jinan Fifth People’s Hospital, Jinan, Shandong Province, China
    5 Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
  • Received:2017-08-20 Online:2017-10-15 Published:2017-10-15
  • Contact: Yi Xing, M.D., Ph.D.,xingyi2016@yahoo.com.
  • Supported by:

    This work was supported by the Natural Science Foundation of Shandong Province of China, No. ZR2014HQ065; a grant from the Medical Science and Technology Development Project of Shandong Province of China, No. 2015WS0445.

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Abstract:

Ciliary neurotrophic factor has neuroprotective effects mediated through signal transducer and Janus kinase (JAK) 2/activator of transcription 3 (STAT3) and phosphatidylinositol 3-kinase (PI3K)/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 PI3K/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 PI3K inhibitor LY294002 blocked the neuroprotective effect of ciliary neurotrophic factor. These data indicate that the two pathways JAK2/STAT3 and PI3K/Akt play major roles in mediating the in vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity.

Key words: nerve regeneration, ciliary neurotrophic factor, JAK2/STAT3, PI3K/Akt, glutamate, neuron, excitotoxicity, neuroprotection, growth-associated protein 43, neurite outgrowth, dorsal root ganglion, neural regeneration