The Relationship Between BDNF and the Wnt Signaling Pathway in the Growth of Human Neural Stem Cell

The first and second author contributed equally to this work.Objective: To clarify that BDNF promotes the growth of human neural stem cell possibly through cross-talk with Wnt/β-catenin signaling pathway.Background: Brain-derived neurotrophic factor (BDNF) plays an important role in promoting the survival, differentiation and proliferation of neural stem cells (NSCs). However, its downstream regulatory convergence with the Wnt/β-catenin signaling pathway in human embryonic spinal cord NSCs (hESC-NSCs) in vitro has not been characterized.Methods: We employ hESC-NSC culture, immunofluoresence labeling, BDNF plasmid transfection, siRNA interference, RT-PCR, real-time PCR and Western blotting to characterize human neural stem cell.Results: We found that the growths of hESC-NSCs were increased after transfection with pIRES2-ZsGreen1-BDNF. Real-time PCR and Western blotting analyses showed that the expression of Wnt, Frizzled, and Dsh were up-regulated, whereas GSK-3β expression was down-regulated. In contrast, the opposite effect on cultured hESC-NSCs was observed after BDNF siRNA interference. However, the expression of PLC-γ and CaM showed no notable changes.Conclusions: The results from this study indicate that BDNF contributes to the growth of hESC-NSCs in vitro, possibly through cross-talk with Wnt/β-catenin signaling pathway.Study Supported by: Natural Science Foundation of China (30960156;31260253); Priority Union Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University (2012FB002); Special Major Foundation of Education Department of Yunnan Province (ZD2013002); Science Foundation of Yunnan Province Education Department (2012J007;2012z151c). Disclosure: Dr. Li has nothing to disclose. Dr. Ma has nothing to disclose. Dr. Yang has nothing to disclose. Dr. Ru has nothing to disclose. Dr. Ren has nothing to disclose. Dr. Gao has nothing to disclose. Dr. Li has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Luo has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Cheng has nothing to disclose. Dr. Guo has nothing to disclose.