PMID- 25051506 OWN - NLM STAT- MEDLINE DCOM- 20150522 LR - 20211021 IS - 1791-3004 (Electronic) IS - 1791-2997 (Print) IS - 1791-2997 (Linking) VI - 10 IP - 4 DP - 2014 Oct TI - Combined effect of nerve growth factor and brain‑derived neurotrophic factor on neuronal differentiation of neural stem cells and the potential molecular mechanisms. PG - 1739-45 LID - 10.3892/mmr.2014.2393 [doi] AB - 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 beta-tubulin III-positive cells and p-ERK expression levels were highest in the NGF + BDNF combination group at all time points. The proportion of beta-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. FAU - Liu, Feifei AU - Liu F AD - Department of Human Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China. FAU - Xuan, Aiguo AU - Xuan A AD - Department of Human Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China. FAU - Chen, Yan AU - Chen Y AD - Department of Human Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China. FAU - Zhang, Jundu AU - Zhang J AD - Department of Human Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China. FAU - Xu, Liping AU - Xu L AD - Department of Human Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China. FAU - Yan, Qijiang AU - Yan Q AD - Kingmed Diagnostics College, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China. FAU - Long, Dahong AU - Long D AD - Department of Human Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140718 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Ascl1 protein, rat) RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Flavonoids) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Messenger) RN - 0 (Tubulin) RN - 0 (neurogenin-1, rat) RN - 169238-82-8 (Neurogenic differentiation factor 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cell Differentiation/*drug effects MH - Cells, Cultured MH - Embryo, Mammalian/cytology MH - Female MH - Flavonoids/pharmacology MH - MAP Kinase Signaling System/drug effects MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Nerve Growth Factors/*pharmacology MH - Nerve Tissue Proteins/genetics/metabolism MH - Neural Stem Cells/cytology/*drug effects/metabolism MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Tubulin/metabolism PMC - PMC4148384 EDAT- 2014/07/23 06:00 MHDA- 2015/05/23 06:00 PMCR- 2014/07/18 CRDT- 2014/07/23 06:00 PHST- 2014/02/14 00:00 [received] PHST- 2014/03/11 00:00 [accepted] PHST- 2014/07/23 06:00 [entrez] PHST- 2014/07/23 06:00 [pubmed] PHST- 2015/05/23 06:00 [medline] PHST- 2014/07/18 00:00 [pmc-release] AID - mmr-10-04-1739 [pii] AID - 10.3892/mmr.2014.2393 [doi] PST - ppublish SO - Mol Med Rep. 2014 Oct;10(4):1739-45. doi: 10.3892/mmr.2014.2393. Epub 2014 Jul 18.