PMID- 28524001 OWN - NLM STAT- MEDLINE DCOM- 20180718 LR - 20180718 IS - 1996-3181 (Electronic) IS - 1871-5273 (Linking) VI - 16 IP - 7 DP - 2017 TI - Brain-derived Neurotrophic Factor Promotes Growth of Neurons and Neural Stem Cells Possibly by Triggering the Phosphoinositide 3-Kinase/ AKT/Glycogen Synthase Kinase-3beta/beta-catenin Pathway. PG - 828-836 LID - 10.2174/1871527316666170518170422 [doi] AB - BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a crucial role in promoting survival and differentiation of neurons and neural stem cells (NSCs), but the downstream regulating mechanisms remain poorly understood. OBJECTIVE: We investigated whether BDNF exerts its effect by triggering the phosphoinositide 3-kinase (PI3K), protein kinase B, PKB (AKT), glycogen synthase kinase-3beta (GSK-3beta) and beta-catenin signaling pathway in cultured neurons and NSCs derived from the rat embryonic spinal cord. METHOD: Immunocytochemistry was used to detect neuronal and NSCs characteristics. RT-PCR was used to detect PI3K/AKT/GSK3beta/beta-catenin pathway expression. RESULTS: Neurons and NSCs were successfully separated and cultured from Sprague-Dawley rat embryonic spinal cord and were respectively labeled using immunocytochemistry. Neuron-specific nuclear protein, neuronal class III beta-tubulin, and neurofilament expression were detected in neurons; nestin, glial fibrillary acidic protein, microtubule-associated protein 2 and chondroitin sulfate glycosaminoglycan expression were detected in the NSCs. BDNF promoted significant neuronal growth (number, soma size, and average neurite length), as well as NSCs proliferation and differentiation, but BDNF antibody decreased neuronal growth and NSCs proliferation and differentiation. RT-PCR was used to detect changes in BDNF signal pathway components, showing that BDNF upregulated tropomyosin receptor kinase B, phosphoinositide 3-kinase (PI3K), AKT and beta-catenin, but downregulated GSK-3beta in the neurons and NSCs. BDNF antibody downregulated BDNF, tropomyosin receptor kinase B, PI3K, AKT, beta-catenin and cellular-myelocytomatosis viral oncogene, but upregulated GSK- 3beta, in the neurons and NSCs. CONCLUSION: Our findings suggested that BDNF contributed to neuronal growth and proliferation and differentiation of NSCs in vitro by stimulating PI3K/AKT/GSK3beta/beta-catenin pathways. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. FAU - Li, Xing-Tong AU - Li XT AD - Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500. China. FAU - Liang, Zhang AU - Liang Z AD - Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500. China. FAU - Wang, Tong-Tong AU - Wang TT AD - Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500. China. FAU - Yang, Jin-Wei AU - Yang JW AD - Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500. China. FAU - Ma, Wei AU - Ma W AD - Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500. China. FAU - Deng, Shi-Kang AU - Deng SK AD - Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500. China. FAU - Wang, Xian-Bin AU - Wang XB AD - Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500. China. FAU - Dai, Yun-Fei AU - Dai YF AD - Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650500. China. FAU - Guo, Jian-Hui AU - Guo JH AD - Second Department of General Surgery, First People's Hospital of Yunnan Province, Kunming, Yunnan. China. FAU - Li, Li-Yan AU - Li LY AD - Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan. China. LA - eng PT - Journal Article PL - United Arab Emirates TA - CNS Neurol Disord Drug Targets JT - CNS & neurological disorders drug targets JID - 101269155 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (beta Catenin) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/*physiology MH - Cell Division MH - Cells, Cultured MH - Glycogen Synthase Kinase 3 beta/*metabolism MH - Neural Stem Cells/*enzymology/*physiology MH - Neurogenesis/*physiology MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Rats MH - Signal Transduction/*physiology MH - beta Catenin/metabolism OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - PKB OT - glycogen synthase kinase-3beta OT - neural stem cells OT - neurons OT - phosphoinositide 3-kinase OT - protein kinase B OT - beta-catenin EDAT- 2017/05/20 06:00 MHDA- 2018/07/19 06:00 CRDT- 2017/05/20 06:00 PHST- 2017/01/19 00:00 [received] PHST- 2017/03/07 00:00 [revised] PHST- 2017/05/01 00:00 [accepted] PHST- 2017/05/20 06:00 [pubmed] PHST- 2018/07/19 06:00 [medline] PHST- 2017/05/20 06:00 [entrez] AID - CNSNDDT-EPUB-83560 [pii] AID - 10.2174/1871527316666170518170422 [doi] PST - ppublish SO - CNS Neurol Disord Drug Targets. 2017;16(7):828-836. doi: 10.2174/1871527316666170518170422.