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.

Parkinson's disease, aging and adult neurogenesis: Wnt/β‐catenin signalling as the key to unlock the mystery of endogenous brain repair

“…Bdnf ) expression (Zhang, Zhang, Deng, et al, ; Zhang, Shi, et al, ; Zhang, Zhang, Yang, et al, ). Also, in human NSCs, Yang et al () showed the ability of BDNF to promote their growth via GSK‐3β‐mediated crosstalk with the WβC‐ signalling pathway, and Li et al () involved the contribution of the PI3K/Akt/GSK‐3β/β‐catenin pathway in BDNF‐induced neuron and NSC growth. Ambrosone et al () documented the ability of optogenetic stimulation to promote cell proliferation and the migration of SVZ neuroblasts into the peri‐infarct cortex, asssociated with increased neuronal differentiation and improvement of long‐term functional recovery after stroke.…”

“…Physical activity and environmental enrichment regulate the generation of neural precursors in the adult mouse substantia nigra; WβC-AC involvement to be elucidated Klaissle et al (2012) Endurance exercise promotes neuroprotection against MPTP injury via enhanced neurogenesis, antioxidant capacity and autophagy; WβC-AC involvement to be elucidated Jang, kwon, Song, Cosio-Lima and Lee (2018a), Jang et al (2018b) Neural activation Neural activity-induced WβC-AC up-regulates expression of BDNF. Zhang, Zhang, Deng, et al, 2018a Neurotrophic factors BDNF promotes growth of neurons and NSCs, possibly through activation of the PI3K/GSK-3β/β-catenin pathway Li et al (2017) BDNF promotes human neural stem cell growth via GSK-3β-mediated crosstalk with the WβC pathway Yang et al (2016) Optical depolarization…”

Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats

“… 22 , 23 Although the underlying mechanisms remain unknown, it has been reported that BDNF appears to be a direct target of Wnt signaling. 24 Together with the fact that the canonical Wnt signaling pathway has been reported to be implicated in mood disorders such as bipolar disorder and major depression, 25 , 26 the protein expression levels of BDNF and the Wnt/β-catenin pathway were further investigated in CUMS rats in the present study.…”

The critical role of EGF-β-catenin signaling in the epithelial-mesenchymal transition in human glioblastoma

“…Recently, increasing reports demonstrated that activation of Wnt/β-catenin signaling and increased β-catenin expression is involved in the development of gliomas,7 and some signaling pathways can regulate Wnt/β-catenin signaling to participate in cell apoptosis,7 human neural stem cell growth,8 glioma cell proliferation,9,10 and glioma cell cycle 10. Based on the molecular level, Wnt/β-catenin signaling can up-regulate many kinds of cell cycle-related regulators, involving cyclin D1 and cyclin E, and down-regulate cell cycle-related inhibitors, like p21 and p27 11.…”