title: Etifoxine promotes glial‑derived neurotrophic factor‑induced neurite outgrowth in PC12 cells.
abstract: Nerve regeneration and functional recovery are major issues following nerve tissue damage. Etifoxine is currently under investigation as a therapeutic strategy for promoting neuroprotection, accelerating axonal regeneration and modulating inﬂammation. In the present study, a well‑defined PC12 cell model was used to explore the underlying mechanism of etifoxine‑stimulated neurite outgrowth. Etifoxine was found to promote glial‑derived growth factor (GDNF)‑induced neurite outgrowth in PC12 cells. Average axon length increased from 50.29±9.73 to 22.46±5.62 µm with the use of etifoxine. However, blockage of GDNF downstream signaling was found to lead to the loss of this phenomenon. The average axon length of the etifoxine group reduces to a normal level after the blockage of the GDNF family receptor α1 (GFRα1) and receptor tyrosine kinase (RETS) receptors (27.46±3.59 vs. 22.46±5.62 µm and 25.31±3.68 µm vs. 22.46±5.62 µm, respectively, p>0.05). In addition, etifoxine markedly increased GDNF mRNA and protein expression (1.55‑ and 1.36-fold, respectively). However, blockage was not found to downregulate GDNF expression. The results of the current study demonstrated that etifoxine stimulated neurite outgrowth via GDNF, indicating that GDNF represents a key molecule in etifoxine‑stimulated neurite outgrowth in PC12 cells.
authors.affiliation: Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.forename: Xinhua
authors.initials: X
authors.lastname: He
authors.forename: Bo
authors.initials: B
authors.lastname: He
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Zhu
authors.forename: Canbin
authors.initials: C
authors.lastname: Zheng
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Liqiang
authors.initials: L
authors.lastname: Gu
authors.forename: Jiakai
authors.initials: J
authors.lastname: Zhu
authors.forename: Qingtang
authors.initials: Q
authors.lastname: Zhu
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism*; D010078:Oxazines / Q000494:pharmacology*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D014151:Anti-Anxiety Agents; D051100:Glial Cell Line-Derived Neurotrophic Factor; D010078:Oxazines; D012333:RNA, Messenger; C002125:etifoxine