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

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.

Diet‐Induced Paternal Obesity Impairs Cognitive Function in Offspring by Mediating Epigenetic Modifications in Spermatozoa

“…Previous studies have demonstrated correlations between hippocampal neurogenesis and cognitive function (28)(29)(30). Furthermore, studies have revealed that BDNF mediates cell proliferation and survival via its receptor TrkB by activating two main intracellular pathways: the RAS/ERK pathway and the PI3K/AKT pathway (22,23). Consistently, we demonstrate that BDNF/TrkB signaling is associated with cognitive impairments in HFD-fed F1 offspring.…”

Effects of neural stem cell transplantation in Alzheimer’s disease models

“…After transplantation, NSCs differentiate into neurons and/or glial cells and release trophic factors. Asymmetric NSC division generates different cell types that replace damaged neurons [29,30] and the neurotrophic factors released from both differentiated cells and stem cells are related to rapid differentiation [31] and play a significant role in neuroprotection to rescue synaptic density [32][33][34]. Secretion of neurotrophic factors and cell restoration has been shown to improve individual memory function [35,36].…”

Cell‐Surface Expression Levels Are Important for Fine‐Tuning the Performance of Receptor Tyrosine Kinase‐Based Signalobodies

“…For instance, basic fibroblast growth factor (bFGF) is essential for maintaining human embryonic stem cells, whereas vascular endothelial growth factor (VEGF) induces differentiation into endothelial cells . In neural stem cells, epidermal growth factor (EGF) and bFGF are required for self‐renewal, whereas nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) trigger differentiation into neurons . Macrophage colony‐stimulating factor (M‐CSF) plays important roles for growth and migration in macrophages, while insulin not only regulates differentiation of adipocytes but also triggers glucose uptake of adipose and muscle tissues .…”