Etifoxine promotes glial‑derived neurotrophic factor‑induced neurite outgrowth in PC12 cells

Zhou,Xiang; He,Xinhua; He,Bo; Zhu,Zhaowei; Zheng,Canbin; Xu,Jian; Jiang,Li; Gu,Liqiang; Zhu,Jiakai; Zhu,Qingtang; Liu,Xiaolin

doi:10.3892/mmr.2013.1474

Etifoxine promotes glial‑derived neurotrophic factor‑induced neurite outgrowth in PC12 cells

Authors:
- Xiang Zhou
- Xinhua He
- Bo He
- Zhaowei Zhu
- Canbin Zheng
- Jian Xu
- Li Jiang
- Liqiang Gu
- Jiakai Zhu
- Qingtang Zhu
- Xiaolin Liu
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Affiliations: Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Physiology, Shangtou University Medical College, Shantou, Guangdong 515041, P.R. China, Department of Reproductive Medicine, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China
Published online on: May 13, 2013 https://doi.org/10.3892/mmr.2013.1474
Pages: 75-80

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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.

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