Combined effect of nerve growth factor and brain‑derived neurotrophic factor on neuronal differentiation of neural stem cells and the potential molecular mechanisms

Liu,Feifei; Xuan,Aiguo; Chen,Yan; Zhang,Jundu; Xu,Liping; Yan,Qijiang; Long,Dahong

doi:10.3892/mmr.2014.2393

Combined effect of nerve growth factor and brain‑derived neurotrophic factor on neuronal differentiation of neural stem cells and the potential molecular mechanisms

Authors:
- Feifei Liu
- Aiguo Xuan
- Yan Chen
- Jundu Zhang
- Liping Xu
- Qijiang Yan
- Dahong Long
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Affiliations: Department of Human Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China, Kingmed Diagnostics College, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China
Published online on: July 18, 2014 https://doi.org/10.3892/mmr.2014.2393
Pages: 1739-1745
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Neural stem cells (NSCs) are important pluripotent stem cells, which have potential applications in cell replacement therapy. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been demonstrated to exert a marked impact on the proliferation and differentiation of NSCs. The effects of NGF, BDNF, and BDNF combined with NGF on NSC neuronal differentiation and the possible mechanisms for these effects were investigated in this study. An adherent monolayer culture was employed to obtain highly homogeneous NSCs. The cells were divided into four groups: Control, NGF, BDNF and combination (BDNF + NGF) groups. Neuron differentiation was examined using immunocytochemistry and phospho-extracellular signal‑regulated kinase (p‑ERK) levels were analyzed using western blotting. Reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the HES1, HES5, MASH1, NGN1 and NeuroD transcription factors at different time intervals following neurotrophin‑induced differentiation. NGF and BDNF were observed to induce NSC neuronal differentiation, and β-tubulin III-positive cells and p-ERK expression levels were highest in the NGF + BDNF combination group at all time points. The proportion of β-tubulin Ⅲ‑positive neurons in each group was associated with the expression levels of MASH1, NGN1 and NeuroD in the group. In conclusion, BDNF combined with NGF significantly improved NSC neuronal differentiation, which may provide support for the practical application of NSCs in neurodegenerative diseases.

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