神经生长因子和脑源性神经营养因子对神经干细胞神经元分化的联合作用及其潜在分子机制。,Molecular Medicine Reports

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神经生长因子和脑源性神经营养因子对神经干细胞神经元分化的联合作用及其潜在分子机制。
Molecular Medicine Reports ( IF 3.4 ) Pub Date : 2014-07-18 , DOI: 10.3892/mmr.2014.2393
Feifei Liu ₁ , Aiguo Xuan ₁ , Yan Chen ₁ , Jundu Zhang ₁ , Liping Xu ₁ , Qijiang Yan ₂ , Dahong Long ₁

Affiliation

神经干细胞（NSCs）是重要的多能干细胞，在细胞替代治疗中具有潜在的应用价值。脑源性神经营养因子（BDNF）和神经生长因子（NGF）已被证明对神经干细胞的增殖和分化产生显着影响。本研究探讨了 NGF、BDNF 和 BDNF 与 NGF 联合对 NSC 神经元分化的影响以及这些影响的可能机制。采用贴壁单层培养获得高度均匀的神经干细胞。细胞分为四组：对照、NGF、BDNF和组合（BDNF + NGF）组。使用免疫细胞化学检查神经元分化，并使用蛋白质印迹分析磷酸化细胞外信号调节激酶 (p-ERK) 水平。逆转录聚合酶链反应用于测量神经营养因子诱导分化后不同时间间隔的 HES1、HES5、MASH1、NGN1 和 NeuroD 转录因子的 mRNA 表达水平。观察到 NGF 和 BDNF 诱导 NSC 神经元分化，在所有时间点，NGF + BDNF 组合组中 β-微管蛋白 III 阳性细胞和 p-ERK 表达水平最高。各组β-微管蛋白Ⅲ阳性神经元比例与该组MASH1、NGN1和NeuroD的表达水平相关。综上所述，BDNF联合NGF显着改善了NSC神经元分化，这可能为NSCs在神经退行性疾病中的实际应用提供支持。神经营养因子诱导分化后不同时间间隔的 NGN1 和 NeuroD 转录因子。观察到 NGF 和 BDNF 诱导 NSC 神经元分化，在所有时间点，NGF + BDNF 组合组中 β-微管蛋白 III 阳性细胞和 p-ERK 表达水平最高。各组β-微管蛋白Ⅲ阳性神经元比例与该组MASH1、NGN1和NeuroD的表达水平相关。综上所述，BDNF联合NGF显着改善了NSC神经元分化，这可能为NSCs在神经退行性疾病中的实际应用提供支持。神经营养因子诱导分化后不同时间间隔的 NGN1 和 NeuroD 转录因子。观察到 NGF 和 BDNF 诱导 NSC 神经元分化，在所有时间点，NGF + BDNF 组合组中 β-微管蛋白 III 阳性细胞和 p-ERK 表达水平最高。各组β-微管蛋白Ⅲ阳性神经元比例与该组MASH1、NGN1和NeuroD的表达水平相关。综上所述，BDNF联合NGF显着改善了NSC神经元分化，这可能为NSCs在神经退行性疾病中的实际应用提供支持。在所有时间点，NGF + BDNF 组合组的 β-微管蛋白 III 阳性细胞和 p-ERK 表达水平最高。各组β-微管蛋白Ⅲ阳性神经元比例与该组MASH1、NGN1和NeuroD的表达水平相关。综上所述，BDNF联合NGF显着改善了NSC神经元分化，这可能为NSCs在神经退行性疾病中的实际应用提供支持。在所有时间点，NGF + BDNF 组合组的 β-微管蛋白 III 阳性细胞和 p-ERK 表达水平最高。各组β-微管蛋白Ⅲ阳性神经元比例与该组MASH1、NGN1和NeuroD的表达水平相关。综上所述，BDNF联合NGF显着改善了NSC神经元分化，这可能为NSCs在神经退行性疾病中的实际应用提供支持。

"点击查看英文标题和摘要"

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

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.

更新日期：2019-11-01

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