title: BDNF promotes the growth of human neurons through crosstalk with the Wnt/β-catenin signaling pathway via GSK-3β.
abstract: Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal growth; however, the downstream regulatory mechanisms remain unclear. In this study, we investigated whether BDNF exerts its neurotrophic effects through the Wnt/β-catenin signaling pathway in human embryonic spinal cord neurons in vitro. We found that neuronal growth (soma size and average neurite length) was increased by transfection with a BDNF overexpression plasmid. Western blotting and real-time quantitative PCR showed that expression of the BDNF pathway components TrkB, PI3K, Akt and PLC-γ was increased by BDNF overexpression. Furthermore, the Wnt signaling factors Wnt, Frizzled and Dsh and the downstream target β-catenin were upregulated, whereas GSK-3β was downregulated. In contrast, when BDNF signaling was downregulated with BDNF siRNA, the growth of neurons was decreased. Furthermore, BDNF signaling factors, Wnt pathway components and β-catenin were all downregulated, whereas GSK-3β was upregulated. This suggests that BDNF affects the growth of neurons in vitro through crosstalk with Wnt signaling, and that GSK-3β may be a critical factor linking these two pathways. To evaluate this possibility, we treated neurons with 6-bromoindirubin-3'-oxime (BIO), a small molecule GSK-3β inhibitor. BIO reduced the effects of BDNF upregulation/downregulation on soma size and average neurite length, and suppressed the impact of BDNF modulation on the Wnt signaling pathway. Taken together, our findings suggest that BDNF promotes the growth of neurons in vitro through crosstalk with the Wnt/β-catenin signaling pathway, and that this interaction may be mediated by GSK-3β.
authors: Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500, China; Second Department of General Surgery, First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, China. Electronic address: yangjinwei800908@163.com.
authors: Jin-Wei
authors: JW
authors: Yang
authors: Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500, China; Second Department of General Surgery, First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, China. Electronic address: rujin227@163.com.
authors: Jin
authors: J
authors: Ru
authors: Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500, China. Electronic address: mawei343897745@163.com.
authors: Wei
authors: W
authors: Ma
authors: Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500, China; Department of Pathology, Children's Hospital of Kunming City, Kunming, Yunnan 650034, China. Electronic address: flystaryanzi@163.com.
authors: Yan
authors: Y
authors: Gao
authors: Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500, China. Electronic address: ynkml-z@163.com.
authors: Zhang
authors: Z
authors: Liang
authors: Second Department of General Surgery, First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, China. Electronic address: 791489440@qq.com.
authors: Jia
authors: J
authors: Liu
authors: Second Department of General Surgery, First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, China. Electronic address: guojianhuikm@163.com.
authors: Jian-Hui
authors: JH
authors: Guo
authors: Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500, China. Electronic address: kmliyanl@163.com.
authors: Li-Yan
authors: LY
authors: Li
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010091:Oximes / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: C483321:6-bromoindirubin-3'-oxime; D019208:Brain-Derived Neurotrophic Factor; D007211:Indoles; D010091:Oximes; D012333:RNA, Messenger; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: BDNF; BIO; GSK-3β; Human neuron; Wnt/β-catenin signaling