BDNF promotes human neural stem cell growth via GSK-3β-mediated crosstalk with the wnt/β-catenin signaling pathway

Abstract

Brain-derived neurotrophic factor (BDNF) plays important roles in neural stem cell (NSC) growth. In this study, we investigated whether BDNF exerts its neurotrophic effects through the Wnt/β-catenin signaling pathway in human embryonic spinal cord NSCs (hESC-NSCs) in vitro. We found an increase in hESC-NSC growth by BDNF overexpression. Furthermore, expression of Wnt1, Frizzled1 and Dsh was upregulated, whereas GSK-3β expression was downregulated. In contrast, hESC-NSC growth was decreased by BDNF RNA interference. BDNF, Wnt1 and β-catenin components were all downregulated, whereas GSK-3β was upregulated. Next, we treated hESC-NSCs with 6-bromoindirubin-3′-oxime (BIO), a small molecule inhibitor of GSK-3β. BIO reduced the effects of BDNF upregulation/downregulation on the cell number, soma size and differentiation, and suppressed the effect of BDNF modulation on the Wnt signaling pathway. Our findings suggest that BDNF promotes hESC-NSC growth in vitro through crosstalk with the Wnt/β-catenin signaling pathway, and that this interaction may be mediated by GSK-3β.

• BDNF
• Human neural stem cell
• GSK-3β
• Wnt/β-catenin signaling pathway

Declaration of interest

This work was supported by the Natural Science Foundation of China (NO 30960156, NO 31260253, NO 31560295); Priority Union Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University (NO 2012FB002, NO 2013FB114); Special Major Foundation of Education Department of Yunnan Province (NO ZD2013002); Science Foundation of Education Department of Yunnan Province (NO 2014C020Y).

The authors report no declarations of interest.

Supplementary material available online.

Supplementary Figure 1

Supplementary Tables 1 and 2